Search results for: Wistar
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 214

Search results for: Wistar

64 Contribution of mTOR to Oxidative/Nitrosative Stress via NADPH Oxidase System Activation in Zymosan-Induced Systemic Inflammation in Rats

Authors: Seyhan Sahan-Firat, Meryem Temiz-Resitoglu, Demet Sinem Guden, Sefika Pinar Kucukkavruk, Bahar Tunctan, Ayse Nihal Sari, Zumrut Kocak

Abstract:

We hypothesized that mTOR inhibition may prevent the multiple organ failures following severe multiple tissue injury associated with increased NADPH oxidase system activity occur in zymosan-induced systemic inflammation. Therefore, we investigated the role of mTOR in oxidative/nitrosative stress associated with increase in NADPH oxidase activity in zymosan-induced systemic inflammation model in rats. Male Wistar rats received saline (4 ml/kg, i.p.) and zymosan (500 mg/kg, i.p.) at time 0. Saline, or zymosan-treated rats were given rapamycin (1 mg/kg, i.p.) 1 h after saline or zymosan injections. Rats were sacrified 4 h after zymosan challenge and kidney, heart, thoracic aorta, and superior mesenteric artery were collected. NADPH oxidase activity, p22phox, gp91phox, and p47phox protein expression and nitrotyrosine levels were measured in tissue samples. Zymosan administration caused an increase in NADPH oxidase activity, p22phox, gp91phox, and p47phox protein expression and nitrotyrosine levels in kidney, heart, thoracic aorta, and superior mesenteric artery. These changes caused by zymosan reversed by rapamycin, a selective mTOR inhibitor. Rapamycin alone had no effect on the parameters measured. Our results demonstrated that zymosan-induced oxidative/nitrosative stress presumably due to enhanced activity of NADPH oxidase, expression of p22phox, gp91phox, and p47phox and production of peroxynitrite were mediated by mTOR. [This work was financially supported by Research Foundation of Mersin University (2016-2-AP3-1900)].

Keywords: oxidative stress, mTOR, nitrosative stress, zymosan

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63 Implication of Oxidative Stress and Intracellular Mediators in the Protective Effect of Artemisia campestris against Aspirin-Induced Gastric Lesions in Rat Model

Authors: Hichem Sebai, Mohamed Amine Jabri, Kais Rtibi, Haifa Tounsi, Lamjed Marzouki

Abstract:

Artemisia campestris has been widely used in Tunisian traditional medicine for its health beneficial effects. However, the present study aims at evaluating the antiulcer effects of Artemisia campestris aqueous extract (ACAE) as well as the mechanism of action involved in such gastroprotection. In this respect, male Wistar rats were divided into seven groups: control, aspirin (ASPR), ASPR + various doses of ACAE (100, 200 and 400 mg/kg, b.w.), ASPR+ famotidine and ASPR+ caffeic acid. Animals were pre-treated with ACAE extract during 10 days. We firstly showed that aspirin administration was accompanied by an oxidative stress status assessed by an increase of malondialdehyde (MDA) level, a decrease of sulfhydryl -(SH) groups content and depletion of antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Pre-treatment with ACAE protected against aspirin-induced gastric oxidative stress. More importantly, aspirin administration increased plasma and tissue hydrogen peroxide (H₂O₂), free iron and calcium levels while the ACAE pre-treatment reversed all aspirin-induced intracellular mediators disturbance. The results of the present study clearly indicated that AEAC gastroprotection might be related, at least in part, to its antioxidant properties as well as to various gastric mucosal defense mechanisms, including the protection of gastric sulfhydryls and an opposite effect on some intracellular mediators such as free iron, hydrogen peroxide, and calcium. However, our data confirm the use of Artemisia campestris extracts in the Tunisian traditional folk medicine for the treatment of gastrointestinal diseases.

Keywords: gastric ulcer, Artemisia campestris, oxidative stress, sulfhydryl groups, Fenton reaction, rat

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62 Effects of Garlic and Stevia Extract Following Aerobic Exercise on Hypothalamic Semaphorin 4A and Plexin D1 Genes Expression in High-Fat Diet-Induced Obese Rats

Authors: Sayyed-Javad Ziaolhagh, Mojtaba Hokmabadi

Abstract:

Introduction: Childhood obesity is a serious medical condition that affects children and adolescents even in the central nervous system. Semaphorins also play a role in the inflammatory process of the nervous system. On the other hand, it has been stated that garlic and stevia extracts following aerobic exercise are effective on immune system inflammation in addition to aerobic activity. Materials and Methods: For 15 weeks, 50 3-week-old male Wistar rats were fed with conventional rodent chow for control and a high-fat diet to induce obesity. Obese rats then were randomly assigned into 7 groups (n=5) based on the Lee index: healthy control (C), obese (OBS), obese + garlic (OBS+GAR), obese + Stevia (OBS+STV), obese + aerobic exercise (OBS+EXE), obese + garlic + aerobic exercise (OBS+GAR+EXE), and obese + stevia + aerobic exercise (OBS+STV+EXE). Training groups completed a progressive aerobic running program (at 8-15 m/min, 5-20 min/day, 5 days/week), and Stevia and garlic extract group (250 mg/kg/day, 5 days/week) were given orally once a day. Real-time PCR was used to determine the levels of Semaphorin 4A, and Plexin D1 gene expressions in the hypothalamus. Fold change analysis with ANOVA was performed for statistical analysis, with a significance threshold of P<0.05. Results: Body weight increased significantly in OBS compared to C (p= 0.013), but was not significantly changed in all treatment rats. Moreover, Semaphorin 4A was significantly increased in obese compared to control group (p= 0.041) and after 8 weeks, stevia extract (p=0.006), aerobic exercise (p=0.012) and garlic extract + aerobic exercise (p=0.008) significantly decreased compared to obese rats. In addition, Plexin D1 genes were also found in the hypothalamus of both obese and control rats but were insignificantly up-regulated when compared with the obese group (p=0.950). Conclusion: High-fat diet caused neuroinflammation by elevation of sema4A in obese rats and stevia, stevia with aerobic and garlic with aerobic could reduce this inflammation in rats. Also, none of them could alter Plexin D1.

Keywords: sema 4A, plexin D1, garlic, stevia

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61 Broccoli Sprouts Powder Could Improve Metabolic and Liver Disorder-Induced by High-Fructose Corn Syrup

Authors: Zahra Bahadoran, Parvin Mirmiran, Hanieh-Sadat Ejtahed, Maryam Tohidi, Fereidoun Azizi

Abstract:

Background and Aim: Broccoli sprouts, rich source of bioactive compounds specially sulforaphane (SFN), have unique functional properties. This study was conducted to investigate the possible treatment effects of high-SFN broccoli sprouts powder on metabolic and liver disorders in rats fed with high-fructose corn syrup. Methods: Thirty-two male wistar rats, pretreated with an eight-week high-fructose diet (water containing 30% fructose), were randomly allocated into three groups: Baseline control (BC), control (C) (normal diet), and BSP-diet (normal diet+5% BSP). The duration of the study was 6 weeks. Biochemical measurements, liver weight and triglyceride content were evaluated and histopathological examination of liver was performed. Results: After 6-weeks, the liver weight was significantly lower in BSP group compared to controls (13.4 g vs. 11.4 g, P<0.05). After 6 weeks, a significant decrease was observed in fasting serum glucose, total cholesterol and triglyceride levels in both experimental groups (P<0.05). Compared to controls, serum levels of HDL-C were significantly higher in BSP group. The liver TG content in BSP compared to control group was lower (14.6 vs. 16.4 mg/mg tissue). The hepatic levels of alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transferase had not considerable changes in the groups after the intervention period but the level of alkaline phosphatase significantly decreased in BSP group (P<0.05). The histopathological examination of liver confirmed a decrease lobular and portal inflammation and ballooning in BSP group compared to control. Conclusion: High-SFN broccoli sprouts powder has beneficials effect on metabolic and liver changes-induced by high fructose corn syrup.

Keywords: broccoli sprouts, metabolic disorders, fatty liver, food science

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60 Formulation, Nutritive Value Assessment And Effect On Weight Gain Of Infant Formulae Prepared From Locally Available Materia

Authors: J. T. Johnson, R. A. Atule, E. Gbodo

Abstract:

The widespread problem of infant malnutrition in developing countries has stirred efforts in research, development and extension by both local and international organizations. As a result, the formulation and development of nutritious weaning foods from local and readily available raw materials which are cost effective has become imperative in many developing countries. Thus, local and readily available raw materials where used to compound and develop nutritious new infant formulae. The materials used for this study include maize, millet, cowpea, pumpkin, fingerlings, and fish bone. The materials where dried and blended to powder. The powders were weighed in the ratio of 4:4:4:3:1:1 respectively and were then mixed properly. Analysis of nutritive value was conducted on the formulae and compared with NAN-2 standard and results reveals that the formulae had reasonable amount of moisture, lipids, carbohydrate, protein, and fibre. Although NAN-2 was superior in both carbohydrate and protein, the new infant formula was higher in mineral elements, vitamins, fibre, and lipids. All the essentials vitamins and both macro and micro minerals where found in appreciable quantity capable of meeting the biochemical and physiological demand of the body while the anti-nutrients composition were significantly below FAO and WHO safe limits. Finally, the compounded infant formulae was feed to a set of albino Wistar rats while some other set of rats was feed with NAN-2 for the period of twenty seven (27) days and body weight was measure at three days intervals. The results of body weight changes was spectacular as their body weight over shot or almost double that of those animals that were feed with NAN-2 at each point of measurement. The results suggest that the widespread problem of infant malnutrition in the developing world especially among the low income segment of the society can now be reduced if not totally eradicated since nutritive and cost effective weaning formulae can be prepared locally from common readily available materials.

Keywords: formulation, nutritive value, local, materials

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59 Anti-Obesity Activity of Garcinia xanthochymus: Biochemical Characterization and In vivo Studies in High Fat Diet-Rat Model

Authors: Mahesh M. Patil, K. A. Anu-Appaiah

Abstract:

Overweight and obesity is a serious medical problem, increasing in prevalence, and affecting millions worldwide. Investigators have been trying from decades to articulate the burden of obesity and related risk factors. To answer this problem, we suggest a new therapeutic anti-obesity compounds from Garcinia xanthochymus fruit. However, there is little published scientific information on non-hydroxycitric acid Garcinia species. Our findings include biochemical characterization of the fruit; in vivo toxicity and bio-efficacy study of G. xanthochymus in high fat diet wistar rat model. We observed that Garcinia pericarp is a rich source of organic acids, polyphenols, mono- (40.63%) and poly-unsaturated fatty acids (16.45%; omega-3: 10.02%). Toxicological studies have showed that Garcinia is safe and had no observed adverse effect level up to 400 mg/kg/day. Body weight and food intake was significantly (P<0.05) reduced in oral gavage treated rats (sonicated Garcinia powder) in 13 weeks. Subcutaneous fat was significantly (P<0.05) reduced in Garcinia treated rats. Hepatocytes significantly (p<0.05) overexpressed sterol regulatory element binding protein 2, liver X receptor- α, liver X receptor- β, lipoprotein lipase and monoacylglycerol lipase. Fatty acid binding protein 1 and peroxisome proliferator activated receptor- α were down regulated as assessed by real time qPCR. Currently our research is focused on the adipocyte obesity related gene expressions, effect of Garcinia on 3T3-adipocyte cell lines and high fat diet induced mice model. This in vivo pre-clinical data suggests that G. xanthochymus may have clinical utility for the treatment of obesity. However, further studies are required to establish its potency.

Keywords: Garcinia xanthochymus, anti-obesity, high fat diet, real time qPCR

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58 Antioxydant Properties and Gastroprotective Effect of Rosa canina Aqueous Extract against Alcohol-Induced Ulceration and Oxidative Stress in Rat Model

Authors: H. Sebai, M. A. Jabria, D. Wannes, H. Tounsi, L. Marzouki

Abstract:

We aimed in the present study to investigate the protective effects of Tunisian Rosa canina aqueous extract (RCAE) against ethanol-induced gastric ulceration and oxidative stress in a rat model. In this respect, adult male Wistar rats were used and divided into six groups of ten each: control, EtOH, EtOH plus various doses of RCAE, EtOH plus famotidine and EtOH + gallic acid. Phytochemical and biochemical analysis were performed using colorimetric methods. We found that RCAE is rich in total polyphenols, total flavonoids, and condensed tannins, and exhibited an importance in vitro antioxidant activity on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. In vivo, the results showed that oral administration of EtOH caused macroscopic and histological changes in gastric mucosa. These injuries are accompanied by an oxidative stress status as assessed by an increase of lipid peroxidation as well as a decrease of antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Alcohol intoxication also induced intracellular mediators deregulation as assessed by an increase of hydrogen peroxide (H2O2), calcium and free iron levels in gastric mucosa. More, importantly, RCAE pretreatment reversed all macroscopic, histological and biochemical changes induced by EtOH administration. In conclusion, we suggest that RCAE has potent protective effects on acute ethanol-induced gastric ulceration related in part in part its antioxidant properties and its opposite effect on intracellular mediators. Indeed, Rosa canina can be offered as a food additive to protect against alcohol consumption-induced gastric and oxidative damage.

Keywords: alcohol, antioxidant properties, food additive, gastric ulceration, rat model, Rosa canina

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57 Neuroprotective Effect of Tangeretin against Potassium Dichromate-Induced Acute Brain Injury via Modulating AKT/Nrf2 Signaling Pathway in Rats

Authors: Ahmed A. Sedik, Doaa Mahmoud Shuaib

Abstract:

Brain injury is a cause of disability and death worldwide. Potassium dichromate (PD) is an environmental contaminant widely recognized as teratogenic, carcinogenic, and mutagenic towards animals and humans. The aim of the present study was to investigate the possible neuroprotective effects of tangeretin (TNG) on PD-induced brain injury in rats. Forty male adult Wistar rats were randomly and blindly allocated into four groups (8 rats /group). The first group received saline intranasally (i.n.). The second group received a single dose of PD (2 mg/kg, i.n.). The third group received TNG (50 mg/kg; orally) for 14 days, followed by i.n. of PD on the last day of the experiment. Four groups received TNG (100 mg/kg; orally) for 14 days, followed by i.n. of PD on the last day of the experiment. 18- hours after the final treatment, behavioral parameters, neuro-biochemical indices, FTIR analysis, and histopathological studies were evaluated. Results of the present study revealed that rats intoxicated with PD promoted oxidative stress and inflammation via an increase in MDA and a decrease in Nrf2 signaling pathway and GSH levels with an increase in brain contents of TNF-α, IL-10, and NF-kβ and reduced AKT levels in brain homogenates. Treatment with TNG (100 mg/kg; orally) ameliorated behavioral, cholinergic activities and oxidative stress, decreased the elevated levels of pro-inflammatory mediators; TNF-α, IL-10, and NF-κβ elevated AKT pathway with corrected FTIR spectra with a decrease in brain content of chromium residues detected by atomic absorption spectrometry. Also, TNG administration restored the morphological changes as degenerated neurons and necrosis associated with PD intoxication. Additionally, TNG decreased Caspase-3 expression in the brain of PD rats. TNG plays a crucial role in AKT/Nrf2 pathway that is responsible for their antioxidant, anti-inflammatory effects, and apoptotic pathway against PD-induced brain injury in rats.

Keywords: tangeretin, potassium dichromate, brain injury, AKT/Nrf2 signaling pathway, FTIR, atomic absorption spectrometry

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56 Antioxidant Potential of Pomegranate Rind Extract Attenuates Pain, Inflammation and Bone Damage in Experimental Rats

Authors: Ritu Karwasra, Surender Singh

Abstract:

Inflammation is an important physiological response of the body’s self-defense system that helps in eliminating and protecting organism from harmful stimuli and in tissue repair. It is a highly regulated protective response which helps in eliminating the initial cause of cell injury, and initiates the process of repair. The present study was designed to evaluate the ameliorative effect of pomegranate rind extract on pain and inflammation. Hydroalcoholic standardized rind extract of pomegranate at doses 50, 100 and 200 mg/kg and indomethacin (3 mg/kg) was tested against eddy’s hot plate induced thermal algesia, carrageenan (acute inflammation) and Complete Freund’s Adjuvant (chronic inflammation) induced models in Wistar rats. Parameters analyzed were inhibition of paw edema, measurement of joint diameter, levels of GSH, TBARS, SOD, TNF-α, radiographic imaging, tissue histology and synovial expression of pro-inflammatory cytokine receptor (TNF-R1). Radiological and light microscopical analysis were carried out to find out the bone damage in CFA-induced chronic inflammatory model. Findings of the present study revealed that pomegranate rind extract at a dose of 200 mg/kg caused a significant (p<0.05) reduction in paw swelling in both the inflammatory models. Nociceptive threshold was also significantly (p<0.05) improved. Immunohistochemical analysis of TNF-R1 in CFA-induced group showed elevated level, whereas reduction in level of TNF-R1 was observed in pomegranate (200 mg/kg). Henceforth, we might say that pomegranate produced a dose-dependent reduction in inflammation and pain along with the reduction in levels of oxidative stress markers and tissue histology, and the effect was found to be comparable to that of indomethacin. Thus, it can be concluded that pomegranate is a potential therapeutic target in the pathogenesis of inflammation and pain, and punicalagin is the major constituents found in rind extract might be responsible for the activity.

Keywords: carrageenan, inflammation, nociceptive-threshold, pomegranate, histopathology

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55 Wharton's Jelly-Derived Mesenchymal Stem Cells Modulate Heart Rate Variability and Improve Baroreflex Sensitivity in Septic Rats

Authors: Cóndor C. José, Rodrigues E. Camila, Noronha L. Irene, Dos Santos Fernando, Irigoyen M. Claudia, Andrade Lúcia

Abstract:

Sepsis induces alterations in hemodynamics and autonomic nervous system (ASN). The autonomic activity can be calculated by measuring heart rate variability (HRV) that represents the complex interplay between ASN and cardiac pacemaker cells. Wharton’s jelly mesenchymal stem cells (WJ-MSCs) are known to express genes and secreted factors involved in neuroprotective and immunological effects, also to improve the survival in experimental septic animals. We hypothesized, that WJ-MSCs present an important role in the autonomic activity and in the hemodynamic effects in a cecal ligation and puncture (CLP) model of sepsis. Methods: We used flow cytometry to evaluate WJ-MSCs phenotypes. We divided Wistar rats into groups: sham (shamoperated); CLP; and CLP+MSC (106 WJ-MSCs, i.p., 6 h after CLP). At 24 h post-CLP, we recorded the systolic arterial pressure (SAP) and heart rate (HR) over 20 min. The spectral analysis of HR and SAP; also the spontaneous baroreflex sensitivity (measure by bradycardic and tachycardic responses) were evaluated after recording. The one-way ANOVA and the post hoc Student– Newman– Keuls tests (P< 0.05) were used to data comparison Results: WJ-MSCs were negative for CD3, CD34, CD45 and HLA-DR, whereas they were positive for CD73, CD90 and CD105. The CLP group showed a reduction in variance of overall variability and in high-frequency power of HR (heart parasympathetic activity); furthermore, there is a low-frequency reduction of SAP (blood vessels sympathetic activity). The treatment with WJ-MSCs improved the autonomic activity by increasing the high and lowfrequency power; and restore the baroreflex sensitive. Conclusions: WJ-MSCs attenuate the impairment of autonomic control of the heart and vessels and might therefore play a protective role in sepsis. (Supported by FAPESP).

Keywords: baroreflex response, heart rate variability, sepsis, wharton’s jelly-derived mesenchymal stem cells

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54 Neuroprotective Effect of Chrysin on Thioacetamide-Induced Hepatic Encephalopathy in Rats: Role of Oxidative Stress and TLR-4/NF-κB Pathway

Authors: S. A. El-Marasy, S. A. El Awdan, R. M. Abd-Elsalam

Abstract:

This study aimed to investigate the possible neuroprotective effect of chrysin on thioacetamide (TAA)-induced hepatic encephalopathy in rats. Also, the effect of chrysin on motor impairment, cognitive deficits, oxidative stress, neuroinflammation, apoptosis and histopathological damage was assessed. Male Wistar rats were randomly allocated into five groups. The first group received the vehicle (distilled water) for 21 days and is considered as normal group. While the second one received intraperitoneal dose of TAA (200 mg/kg) at three alternative days during the third week of the experiment to induce HE and is considered as control group. The other three groups were orally administered chrysin for 21 days (25, 50, 100 mg/kg) and starting from day 17; rats received intraperitoneal dose of TAA (200 mg/kg) at three alternative days. Then behavioral, biochemical, histopathological and immunohistochemical analyses were assessed. Then behavioral, biochemical, histopathological and immunohistochemical analyses were assessed. Chrysin reversed TAA-induced motor coordination in rotarod test, cognitive deficits in object recognition test (ORT) and attenuated serum ammonia, hepatic liver enzymes, reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), reduced nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) brain contents. Chrysin administration also reduced Toll-4 receptor (TLR-4) gene expression, caspase-3 protein expression, hepatic necrosis and astrocyte swelling. This study depicts that chrysin exerted neuroprotective effect in TAA-induced HE rats, evidenced by improvement of cognitive deficits, motor incoordination and histopathological changes such as astrocyte swelling and vacuolization; hallmarks in HE, via reducing hyperammonemia, ameliorating hepatic function, in addition to its anti-oxidant, inactivation of TLR-4/NF-κB inflammatory pathway, and anti-apoptotic effects.

Keywords: chrysin, hepatic encephalopathy, oxidative stress, rats, thioacetamide, TLR4/NF-κB pathway

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53 Emblica officinalis Fruit Extract Ameliorates Cisplatin-Induced Nephrotoxicity in Experimental Rats

Authors: Prerna Kalra, Surender Singh

Abstract:

Cisplatin is the most common chemotherapeutic agent used in different solid tumors, but its main limiting factor is dose-dependent nephrotoxicity by generating reactive oxygen species, by stimulating inflammatory and apoptotic pathways. Additional adjuvant therapies to decrease the toxicity of this chemotherapeutic drug are essential. This study was designed to evaluate the protective role of Emblica officinalis Geartn (Indian gooseberry) against cisplatin induced nephrotoxicity. Emblica officinalis was orally administered to Wistar rats (n=6) for 10 days in 50, 100 and 200mg/kg body weight. On day 7, 8mg/kg of cisplatin was administered intra-peritoneally to rats in all groups. Serum creatinine, blood urea nitrogen and antioxidant levels were measured on day10. The renal damage was evaluated by histopathological and transmission electron microscopy. We found that 200mg/kg dose of Emblica officinalis significantly inhibited the elevation of biochemical parameters i.e. serum creatinine, blood urea nitrogen, oxidant stress marker (malondialdehyde) and increased the reduced levels of antioxidant marker (endogenous glutathione and superoxide dismutase). Cisplatin treated rats have shown acute tubular necrosis and infiltration of inflammatory cells in rat kidney which was reversed after treating the animals with Emblica officinalis in the treatment group. In ultrastructural changes cisplatin treated group showed the damaged mitochondria (M) with dissolved cristae and large number of lysosomes (L) and vacuole (V) formation in tubular epithelial cells. EOE administered group showed visible cristae formation and sign of autophagy vacuoles at a dose of 200mg/kg. Further in-silico studies revealed that ellagic acid is responsible for its nephroprotective effect. The above findings conclude that the Emblica officinalis may be used as an adjuvant therapy in cisplatin induced nephrotoxicity.

Keywords: antioxidant, cisplatin, Emblica officinalis, in silico, nephrotoxicity

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52 Protective Effect of Probiotic Lactic Acid Bacteria on Thioacetamide-Induced Liver Fibrosis in Rats: Histomorphological Study

Authors: Chittapon Jantararussamee, Malai Taweechotipatr, Udomsri Showpittapornchai, Wisuit Pradidarcheep

Abstract:

Hepatic fibrosis is characterized by collagen accumulation in hepatic lobules following wound healing process. If lefts untreated, it could progress into hepatic cirrhosis, portal hypertension, and liver failure. Probiotics comprise of lactic acid bacteria which are crucial components of the intestinal microflora and possess many beneficial properties. The objective of this study is to investigate the hepatoprotective effects of probiotic lactic acid bacteria (mixture of Lactobacillus paracasei, Lactobacillus casei, and Lactobacillus confusus at a ratio of 1: 1: 1) on thioacetamide-induced liver fibrotic rats in term of histomorphology study. Twenty-four male Wistar rats were randomly divided into four groups with 6 rats each: (A) control, (B) fibrotic, (C) fibrotic+probiotic, and (D) probiotic. Group (A) received daily oral administration of distilled water. Group (B and C) were induced by intraperitoneal injection of thioacetamide (TAA) (200 mg/kg BW) 3 times per week for consecutive 8 weeks. In probiotic-treated group (C and D), the number of a mixture of the viable microbial cells at 10⁹ CFU/ml was administered orally daily. After sacrifice, liver tissues were collected and processed for routine histological technique and stained with Sirius red. It was found that the fibrotic rats showed hepatic injury marked by area of inflammation, hydropic degeneration of hepatocytes, and accumulation of myofibroblast-like cells. The collagen fibers were substantially accumulated in the hepatic lobules. Moreover, probiotic-treated group significantly reduced the accumulation of collagen in rats treated by TAA. The liver damage was found to be lesser in the probiotic-treated group. It was noted that the liver tissues of control and probiotics groups were shown to be normal. Administration with probiotic lactic acid bacteria could improve the histomorphology in fibrotic liver and be useful for prevention of hepatic disorders.

Keywords: liver fibrosis, probiotics, lactic acid bacteria, thioacetamide

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51 Development of an Experimental Model of Diabetes Co-Existing with Metabolic Syndrome in Rats

Authors: Rajesh Kumar Suman, Ipseeta Ray Mohanty, Manjusha K. Borde, Ujjawala maheswari, Y. A. Deshmukh

Abstract:

Background: Metabolic syndrome encompasses cluster of risk factors for cardiovascular disease which includes abdominal obesity, dyslipidemia, hypertension, and hyperglycemia. The incidence of metabolic syndrome is on the rise globally. Objective: The present study was designed to develop a unique animal model that will mimic the pathological features seen in a large pool of individuals with diabetes and metabolic syndrome; suitable for pharmacological screening of drugs beneficial in this condition. Material and Methods: A combination of high fat diet (HFD) and low dose of streptozotocin (STZ) at 30, 35 and 40 mg/kg was used to induce metabolic syndrome co-existing with diabetes mellitus in Wistar rats. Results: The 40 mg/kg STZ produced sustained hyperglycemia and the dose was thus selected for our study to induce diabetes mellitus. Rat fed HFD (HF-DC) group showed significant (p < 0.001) increase in body weight on 4th and 7th week as compared with NC (Normal Control) group rats. However, the increase in body weight of HF-DC group rats was not sustained at the end of 10th weeks. Various components of metabolic syndrome such as dyslipidemia {(Increased Triglyceride, total Cholesterol, LDL Cholesterol and decreased HDL Cholesterol)}, diabetes mellitus (Blood Glucose, HbA1c, Serum Insulin, C-peptide), hypertension {Systolic Blood pressure (p < 0.001)} were mimicked in the developed model of metabolic syndrome co existing with diabetes mellitus. In addition significant cardiac injury as indicated by CPK-MB levels, artherogenic index, hs-CRP. The decline in hepatic function {(p < 0.01) increase in the level of SGPT (U/L)} and renal function {(increase in creatinine levels (p < 0.01)} when compared to NC group rats. The histopathological assessment confirmed presence of edema, necrosis and inflammation in Heart, Pancreas, Liver and Kidney of HFD-DC group as compared to NC. Conclusion: The present study has developed a unique rodent model of metabolic syndrome; with diabetes as an essential component.

Keywords: diabetes, metabolic syndrome, high fat diet, streptozotocin, rats

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50 Acrylamide-Induced Thoracic Spinal Cord Axonopathy

Authors: Afshin Zahedi, Keivan Jamshidi

Abstract:

This study was conducted to determine the neurotoxic effects of different doses of ACR on the thoracic axons of the spinal cord of rat. To evaluate this hypothesis in the thoracic axons, amino-cupric silver staining technique of the de Olmos was conducted to define the histopathologic characteristic (argyrophilia) of axonal damage following ACR exposure. For this purpose 60 adult male rats (Wistar, approximately 250 g) were selected. Rats were hosed in polycarbonate boxes as two per each. Randomly assigned groups of rats (10 rats per exposure group, total 5 exposure groups as A, B, C, D and E) were exposed to 0.5, 5, 50, 100 and 500 mg/kg per day×11days intraperitoneal injection (IP injection) respectively. The remaining 10 rats were housed in group (F) as control group. Control rats received daily injections of 0.9% saline (3ml/kg). As indices of developing neurotoxicity, weight gain, gait scores and landing hindlimb foot splay (LHF) were determined. Weight gains were measured daily prior to injection. Gait scoring involved observation of spontaneous open field locomotion, included evaluations of ataxia, hopping, rearing and hind foot placement, and hindlimb foot splay were determined 3-4 times per week. Gait score was assigned from 1-4. After 11 days, two rats for silver stain, were randomly selected, dissected and proper samples were collected from thoracic portion of the spinal cord of rat. Results did show no neurological behavior in groups A, B and F, whereas severe neurotoxicity was observed in groups C and D. Rats in groups E died within 1-2 hours due to severe toxemia. In histopathological studies based on the de Olmos technique no argyrophilic neurons or processes were observed in stained sections obtained from the thoracic portion of the spinal cord of rats belong to groups A, B and F, while moderate to severe argyrophilic changes were observed in different stained sections obtained from the thoracic portion of the spinal cord of rats belong to groups C and D.

Keywords: acrylamide, rat, axonopathy, argyrophily, de Olmos

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49 Positive Effects of Aerobic Exercise after Bone Marrow Stem Cell Transplantation on Recovery of Dopaminergic Neurons and Promotion of Angiogenesis Markers in the Striatum of Parkinsonian Rats

Authors: S. A. Hashemvarzi, A. Heidarianpour, Z. Fallahmohammadi, M. Pourghasem, M. Kaviani

Abstract:

Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative in the central nervous system characterized by the loss of dopaminergic neurons in the substantia nigra resulting in loss of dopamine release in the striatum. Non-drug treatment options such as Stem cell transplantation and exercise have been considered for treatment of Parkinson's disease. Purpose: The purpose of this study was to evaluate the effect of aerobic exercise after bone marrow stem cells transplantation on recovery of dopaminergic neurons and promotion of angiogenesis markers in the striatum of parkinsonian rats. Materials and Methods: 42 male Wistar rats were divided randomly into six groups: Normal (N), Sham (S), Parkinson’s (P), Stem cells transplanted Parkinson’s (SP), Exercised Parkinson’s (EP) and Stem cells transplanted + Exercised Parkinson’s (SEP). To create a model of Parkinson's, the striatum was destroyed by injection of 6-hydroxy-dopamine into the striatum through stereotaxic apparatus. Stem cells were derived from the bone marrow of femur and tibia of male rats with 6-8 weeks old. After cultivation, approximately 5×105 cells in 5 microliter of medium were injected into the striatum of rats through the channel. Aerobic exercise was included 8 weeks of running on the treadmill with a speed of 15 meters per minute. At the end, all subjects were decapitated and striatum tissues were separately isolated for measurement of vascular endothelial growth factor (VEGF), dopamine (DA) and tyrosine hydroxylase (TH) levels. Results: VEGF, DA and TH levels in the striatum of parkinsonian rats significantly increased in treatment groups (SP, EP and SEP), especially in SEP group compared to P group after treatment (P<0.05). Conclusion: The findings implicate that the BMSCs transplantation in combination with exercise would have synergistic effects leading to functional recovery, dopaminergic neurons recovery and promotion of angiogenesis marker in the striatum of parkinsonian rats.

Keywords: stem cells, treadmill training, neurotrophic factors, Parkinson

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48 Protective Efficacy of Moringa oleifera against Oxidative Ovarian Damage and Reproductive Failure in Female Rats Caused by Cyclophosphamide

Authors: Seham Samir Soliman, Ahmed A.Suliman, Khaled Fathy, Ahmed A. Sedik

Abstract:

Cyclophosphamide (CP), an antineoplastic drug, has been found to induce reproductive damage. It is essential to develop approaches aimed at safeguarding ovarian tissue integrity in women experiencing reproductive toxicity as a result of chemotherapy. The current study was conducted to assess the impact of an extract derived from Moringa oleifera (M. oleifera) leaves on ovarian damage produced by CP. A total of 32 female Wistar Albino rats, which were in a healthy cycling state, were randomly separated into 4 groups, with every group contains 8 rats. The first group was administered intraperitoneal (i.p.) saline. The second group was administered a solitary intraperitoneal dosage of cyclophosphamide (200 mg/kg). The third one received M. oleifera extract (150 mg/kg orally) for 20 days, followed by i.p. of CP on the last day of the experiment. The fourth group received M. oleifera extract (250 mg/kg orally) for 20 days, followed by i.p. of CP on the last day of the experiment. Hormonal assessments, including luteinizing hormone (LH), estrogen (ES), and follicle-stimulating hormone (FSH), were performed 24 hours after CP administration. In addition, evaluating the antioxidant status and inflammatory response against CP. Moreover, conducting detailed histopathological and ultra-structural pictures of the ovary. Our findings reported that rats intoxicated with CP exhibited elevated levels of FSH, LH, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and a decrease in E₂, and glutathione (GSH) levels. Pre-treatment with M. oleifera extract (250 mg/kg orally) ameliorated the disturbance in hormonal changes, oxidative stress indices, and the levels of pro-inflammatory mediators. Also, the histopathological and ultra-structural pictures of the ovaries were improved significantly in rats. In conclusion, M. oleifera extract possesses a significant protective role against CP-induced acute reproductive toxicity via modulating the values of FSH, LH, E₂ and quenching the release of reactive oxygen species and inflammatory mediators in female rats.

Keywords: cyclophosphamide, Moringa oleifera, ovarian function, oxidative stress, pro-inflammatory mediators

Procedia PDF Downloads 38
47 Effect of Aquatic Seed Extract of (Cichorium intybus L.) and Metformin on Nitric Oxide in Type 2 Diabetic Rats

Authors: Lotfollah Rezagholizadeh

Abstract:

Background and Aim: Diabetes mellitus is related to high mortality and morbidity caused by the early development of atherosclerosis correlated to diabetic macroangiopathy. The endothelium-derived vasodilator, nitric oxide (NO) has been implicated in the development of vascular complications via the regulation of blood flow, and various antiatherosclerotic actions. Patients with type 2 diabetes (T2D) have a decreased level of endothelial nitric oxide release. In this study we aimed to examine the effect of aquatic seed extract of Cichorium intybus L. (chicory) and metformin (a known prescription drug for diabetes) on NO levels in T2D rats. Methods: Five groups of adult male Wistar rats were used (n=6): Non-diabetic controls without extract treatment (Control), Non-diabetic controls with extract treatment (Chicory-control), T2D rats without extract treatment (NIA/STZ), T2D rats treated with the extract (Chicory-NIA/STZ), and T2D groups that received metformin (100 mg/kg) but no extract (Metformin-NIA/STZ). T2D was induced with intraperitoneal (i.p) injection of niacinamide (NIA, 200 mg/kg), 15 min after an i.p administration of streptozotocin (STZ, 55 mg/kg). Lyophilized chicory extract (125 mg/kg) was dissolved in 0.2 ml normal saline and administered one dose a day. The experiments lasted for 3 weeks after the diabetes induction. NO analysis was performed by assay based on the Griess reaction. Data were reported as the mean ± SD and statistical analysis was performed by ANOVA. Results: Serum nitric oxide levels decreased significantly in NIA/STZ group compared with Control and Chicory-control. Treatment with chicory extract caused a significant increase in serum levels of NO in Chicory-NIA/STZ group compare to NIA/STZ group (p<05). Metformin-NIA/STZ group did not show considerable difference when compared with NIA/STZ, with respect to NO levels. In a group of rats made diabetic by STZ alone (type 1 diabetic rats, T1D), chicory did not have a significant ameliorating effect. Conclusion: In this study, we clearly showed a relationship between low serum nitric oxide levels and diabetes mellitus in rats. The increase in serum nitric oxide by chicory extract is an indication of antiatherogenic effect of this plant. Chicory seed extract was more efficient than metformin in improving the NO levels in NO-deficient T2D diabetic rats.

Keywords: type 2 diabetes mellitus, nitric oxide, chicory, metformin

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46 A Comparative Study on the Hypoglycemic Effects of Hydroalcoholic Extracts from Silybum marianum, Camellia sinensis (Green Tea), and Urtica dioica Plants in Diabetic Rats

Authors: Sogand Moshfeghi, Alireza Biglari

Abstract:

Diabetes is an endocrine disorder that is commonly treated with insulin. However, long-term usage of insulin and hypoglycemic chemical drugs can result in various side effects. Therefore, it is crucial to explore effective compounds with minimal side effects for diabetes treatment. This study aimed to compare the hypoglycemic effects of hydroalcoholic extracts derived from Silybum marianum, Camellia sinensis (green tea), and Urtica dioica plants. Male Wistar rats were allocated to 5 groups. Group 1 received normal Salin. Other groups were diabetic (induced by Streptozotocin 65 mg/kg Ip), group 2 received normal Salin (Ip, qod. 21 days). Group 3 received Silybum Marianum L, hydroalcoholic extract (100 mg/kg, ip.qod, 21 days). Group 4 received Camellia sinesis L, hydroalcoholic extract (100mg/kg,ip,qod,21 days), and group 5 received Urtica dioica L. hydroalcoholic extract (100mg/kg, ip,qod,21 days). Blood samples were collected at 14 and 21 days after the initial injection to evaluate the blood glucose levels. On the fourteenth day, the blood glucose levels for the diabetic groups were as follows: Group 2: 424.7±34.5, Group 3: 390.7±10.5, Group 4: 350.4±16.9, and Group 5: 340±20.5. On the 21st day, the respective blood glucose levels were: Group 2: 432±5.0, Group 3: 410.16±5.0, Group 4: 264.3±17.5, and Group 5: 270.7±24.5. Statistical analysis using the Tukey Anova test indicated that on the fourteenth day, both the green tea and Urtica groups exhibited significant hypoglycemic effects. Furthermore, on the 21st day, Urtica dioica extract demonstrated comparable effects to Camellia Sinensis extract, while Silybum Marianum extract did not significantly lower blood glucose levels compared to the diabetic group. In conclusion, the hydroalcoholic extracts from Camellia sinensis and Urtica dioica plants exhibited promising hypoglycemic effects in diabetic rats. These findings provide valuable insights into the potential use of natural plant extracts as alternative or complementary treatments for diabetes, warranting further investigation to harness their therapeutic benefit effectively.

Keywords: Camellia sinesis, glucose, Silybum marianum, Urtica dioica

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45 Collagen Gel in Hip Cartilage Repair: in vivo Preliminary Study

Authors: A. Bajek, J. Skopinska-Wisniewska, A. Rynkiewicz, A. Jundzill, M. Bodnar, A. Marszalek, T. Drewa

Abstract:

Traumatic injury and age-related degenerative diseases associated with cartilage are major health problems worldwide. The articular cartilage is comprised of a relatively small number of cells, which have a relatively slow rate of turnover. Therefore, damaged articular cartilage has a limited capacity for self-repair. New clinical methods have been designed to achieve better repair of injured cartilage. However, there is no treatment that enables full restoration of it. The aim of this study was to evaluate how collagen gel with bone marrow mesenchymal stem cells (MSCs) and collagen gel alone will influence on the hip cartilage repair after injury. Collagen type I was isolated from rats’ tails and cross-linked with N-hydroxysuccinimide in 24-hour process. MSCs were isolated from rats’ bone marrow. The experiments were conducted according to the guidelines for animal experiments of Ethics Committee. Fifteen 8-week-old Wistar rats were used in this study. All animals received hip joint surgery with a total of 30 created cartilage defects. Then, animals were randomly divided into three groups and filled, respectively, with collagen gel (group 1), collagen gel cultured with MSCs (group II) or left untreated as a control (control group). Immunohistochemy and radiological evaluation was carried out 11 weeks post implantation. It has been proved that the surface of the matrix is non-toxic, and its porosity promotes cell adhesion and growth. However, the in vivo regeneration process was poor. We observed the low integration rate of biomaterial. Immunohistochemical evaluation of cartilage after 11 weeks of treatment showed low II and high X collagen expression in two tested groups in comparison to the control one, in which we observed the high II collagen expression. What is more, after radiological analysis, we observed the best regeneration process in control group. The biomaterial construct and mesenchymal stem cells, as well as the use of the biomaterial itself was not sufficient to regenerate the hip cartilage surfaces. These results suggest that the collagen gel based biomaterials, even with MSCs, are not satisfactory in repar of hip cartilage defect. However, additional evaluation is needed to confirm these results.

Keywords: collafen gel, MSCs, cartilage repair, hip cartilage

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44 Neuroprotective Effect of Vildagliptin against Cerebral Ischemia in Rats

Authors: Salma A. El-Marasy, Rehab F. Abdel-Rahman, Reham M. Abd-Elsalam

Abstract:

The burden of stroke is intensely increasing worldwide. Brain injury following transient or permanent focal cerebral ischemia develops ischemic stroke as a consequence of a complex series of pathophysiological events. The aim of this study is to evaluate the possible neuroprotective effect of a dipeptidyl peptidase-4 inhibitor, vildagliptin, independent on its insulinotropic properties in non-diabetic rats subjected to cerebral ischemia. Anaesthetized Wistar rats were subjected to either left middle cerebral artery occlusion (MCAO) or sham operation followed by reperfusion after 30 min of MCAO. The other three groups were orally administered vildagliptin at 3 dose levels (2.5, 5, 10 mg/kg) for 3 successive weeks before subjected to left focal cerebral ischemia/reperfusion and till the end of the study. Neurological deficit scores and motor activity were assessed 24h following reperfusion. 48h following reperfusion, rats were euthanized and their left brain hemispheres were harvested and used in the biochemical, histopathological, and immunohistochemical investigations. Vildagliptin pretreatment improved neurological score deficit, locomotor activity and motor coordination in MCAO rats. Moreover, vildagliptin reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), phosphotylinosital 3 kinase (PI3K), phosphorylated of protein kinase B (p-AKT), and mechanistic target of rapamycin (mTOR) brain contents in addition to reducing protein expression of caspase-3. Also, vildagliptin showed a dose-dependent attenuation in neuronal cell loss and histopathological alterations in MCAO rats. This study proves that vildagliptin exerted the neuroprotective effect in a dose-dependent manner as shown in amelioration of neuronal cell loss and histopathological damage in MCAO rats, which may be mediated by attenuating neuronal and motor deficits, it’s anti-oxidant property, activation of PI3K/AKT/mTOR pathway and its anti-apoptotic effect.

Keywords: caspase-3, cerebral ischemia, dipeptidyl peptidase-4 inhibitor, oxidative stress, PI3K/AKT/mTOR pathway, rats, vildagliptin

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43 Antidiabetic and Antioxidant Potential of Aqueous Extract of Jasminum humile Leaves in Nicotinamide/Streptozotocin induced Type-2 Diabetes Mellitus (T2DM) Rat

Authors: Parminder Nain, Jaspreet kaur, Vipin Saini, Sunil Sharma

Abstract:

Jasminum humile commonly known as yellow Jasmine or Pili chameli, is a medicinal plant used in Ayurveda for treating various diseases, one of which is diabetes mellitus. The current study aimed to establish the antidiabetic and antioxidant properties of aqueous extract of Jasminum humile leaves (AEJHL) in nicotinamide/streptozotocin induced type 2 diabetic rats. Phytochemical screening, HPLC analysis, and acute toxicity study of AEJHL were carried out. Male albino wistar rats (n=42) were divided into seven equal groups. Rats with moderate diabetes having hyperglycemia (blood glucose 250-400 mg/dl) were taken for the experiment. Various concentrations of aqueous extract of Jasminum humile leaves (50, 100, 200 and 300 mg/kg, p.o.), and glibenclamide (1mg/kg, p.o.) were orally administered to diabetic rats for 45 days. The effect of AEJHL on blood glucose, plasma insulin and biochemical parameters such as hemoglobin, total protein, serum creatinine, serum urea, alkaline phosphate, Glutamic-oxalacetic transaminase (SGOT) and glutamic-pyruvic transaminase (SGPT), as well as total cholesterol, triglycerides, and high-density lipoprotein (HDL) were also studied. The antioxidant effect of AEJHL was determined by analyzing hepatic and renal antioxidant markers, like superoxide dismutase (SOD), catalase (CAT), reduced Glutathione (GSH), Glutathione peroxidase (GPx), and lipid peroxidation (LPO) in diabetic rats. After 45-days oral administration of aqueous extract of Jasminum humile leaves significantly (p<0.05) reduced blood sugar and increase plasma insulin level and also reverse all above biochemical parameters and antioxidant enzyme level at dose dependent manner. These findings provide in vivo evidence that the aqueous extract of Jasminum humile leaves possess significant antidiabetic and antioxidant potential in nicotinamide/streptozotocin-induced type-2 diabetes mellitus in rats.

Keywords: antidiabetic, antioxidant, jasminum humile, nicotinamide/streptozotocin, type-2 diabetic

Procedia PDF Downloads 175
42 Role of Maternal Astaxanthin Supplementation on Brain Derived Neurotrophic Factor and Spatial Learning Behavior in Wistar Rat Offspring’s

Authors: K. M. Damodara Gowda

Abstract:

Background: Maternal health and nutrition are considered as the predominant factors influencing brain functional development. If the mother is free of illness and genetic defects, maternal nutrition would be one of the most critical factors affecting the brain development. Calorie restrictions cause significant impairment in spatial learning ability and the levels of Brain Derived Neurotrophic Factor (BDNF) in rats. But, the mechanism by which the prenatal under-nutrition leads to impairment in brain learning and memory function is still unclear. In the present study, prenatal Astaxanthin supplementation on BDNF level, spatial learning and memory performance in the offspring’s of normal, calorie restricted and Astaxanthin supplemented rats was investigated. Methodology: The rats were administered with 6mg and 12 mg of astaxanthin /kg bw for 21 days following which acquisition and retention of spatial memory was tested in a partially-baited eight arm radial maze. The BDNF level in different regions of the brain (cerebral cortex, hippocampus and cerebellum) was estimated by ELISA method. Results: Calorie restricted animals treated with astaxanthin made significantly more correct choices (P < 0.05), and fewer reference memory errors (P < 0.05) on the tenth day of training compared to offsprings of calorie restricted animals. Calorie restricted animals treated with astaxanthin also made significantly higher correct choices (P < 0.001) than untreated calorie restricted animals in a retention test 10 days after the training period. The mean BDNF level in cerebral cortex, Hippocampus and cerebellum in Calorie restricted animals treated with astaxanthin didnot show significant variation from that of control animals. Conclusion: Findings of the study indicated that memory and learning was impaired in the offspring’s of calorie restricted rats which was effectively modulated by astaxanthin at the dosage of 12 mg/kg body weight. In the same way the BDNF level at cerebral cortex, Hippocampus and Cerebellum was also declined in the offspring’s of calorie restricted animals, which was also found to be effectively normalized by astaxanthin.

Keywords: calorie restiction, learning, Memory, Cerebral cortex, Hippocampus, Cerebellum, BDNF, Astaxanthin

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41 Potency of Strophanthus hispidus Stem Bark in the Management of Streptozotocin-Induced Diabetic Rats

Authors: M. Osibemhe, I. O. Onoagbe

Abstract:

Diabetes mellitus is a common disease that has no known cure. The available orthodox drugs used for its management have one or more disadvantages. This study investigated the potency of aqueous and ethanol extracts of Strophanthus hispidus (SH) stem bark in the management of diabetes mellitus. Glucose concentration and lipid profile parameters of normal and streptozotocin-induced diabetic rats were monitored for 12weeks. Diabetes mellitus was induced by intraperitoneal injection of streptozotocin (55 mg/kg). Male rats (wistar strain) numbering 30 were randomly selected into six groups of five rats each. Groups 1 and 6 served as normal and diabetic control respectively and received distilled water for 12weeks. Groups 2 and 3 were normal rats treated orally with the aid of a gavage, 250 mg/kg of aqueous and ethanol extracts respectively for 12weeks. Groups 4 and 5 were diabetic rats and were treated with the respective dose of aqueous and ethanol extracts for the same period. A significant (P˂0.05) progressive decrease in blood glucose concentrations of both normal and diabetic rats treated with the extracts were observed from the 2nd to 12th weeks when compared with the respective controls. No significant (P˃0.05) effects were observed in the basal values of both normal and diabetic rats. Administration of both extracts of SH to diabetic rats significantly (P˂0.05) lowered the concentrations of Total cholesterol, TG, and LDL, whereas it increases the concentration of HDL when compared with diabetic control. The concentrations of total cholesterol and LDL in normal rats treated with SH were also reduced when compared with normal control whereas SH had no significant (P˃0.05) effect on HDL. However, TG level of normal control was significantly (P˂0.05) lower than normal rats treated with both extracts. A progressive increase in weight of normal and diabetic rats treated with the extracts was observed on the 2nd – 12th weeks of administration, whereas diabetic control showed a progressive decrease in weight. The findings from this study indicated that SH has hypoglycemic and anti-lipidemic properties as well as anti-diabetic potentials. It also showed that ethanol extract had greater glucose lowering effect. Hence, SH may be considered as a potent anti-diabetic plant and could be used as alternative drug for the management of diabetes mellitus.

Keywords: concentration, ethanol extract, hypoglycemic, total cholesterol

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40 Citrullinated Myelin Basic Protein Mediated Inflammation in Astrocytes

Authors: Lali Shanshiashvili, Marika Chikviladze, Nino Mamulashvili, Maia Sepashvili, Nana Narmania, David Mikeladze

Abstract:

Purpose: During demyelinating inflammatory diseases and after the damage of the myelin sheet, myelin-derived proteins, including myelin basic protein (MBP), are secreted into the extracellular space. MBP shows extensive post-translational modifications, including the deimination of arginine residues. Deiminated MBP is structurally less ordered, susceptible to proteolytic attack, and more immunogenic than the unmodified one. It is hypothesized that MBP could change the inflammatory response in astrocytes. Methods: MBP was isolated and purified from bovine brain white matter. Primary astrocyte cultures were prepared from whole brains of 2-day-old Wistar rats. For evaluation of glutamate uptake/release in astrocytes following treatment of cells with MBP charge isomers, Glutamate Assay Kit was used. The expression of EAAT-2 (excitatory amino acid transporters), peroxisome proliferator-activated receptor gamma (PPAR- γ), inhibitor of nuclear factor kappa B (IkB), and high mobility group protein B1 (HMGB1) in astrocytes were assayed by Western Blot analysis. Results: This study investigated the action of deiminated isomer (C8) on the cultured primary astrocytes and compared its effects with the effects of unmodified C1 isomers. The study found that C8 and C1 MBP differently act on the uptake and release of glutamate in astrocytes: nonmodified C1 MBP increases the uptake of glutamate and does not change the release, whereas C8 decreases the release of glutamate but does not alter the uptake. Nevertheless, both isomers increased the expression of PPAR-γ and EAAT2 in the same intensity. However, immunostaining and Western Blots of cell lysates showed a decrease of IkB and increased expression of HMGB1 after the treatment of astrocytes by C8. Moreover, in the presence of C8, astrocytes release more nitric oxide than unmodified C1 isomers. Conclusion: These data suggest that the deiminated isomer of MBP evokes an inflammatory response and enhances the ability of astrocytes to release proinflammatory mediators through activation of NF-kB after the breakdown of myelin sheets. Acknowledgment: This research was supported by the SRNSF Georgia RF17_534 grant.

Keywords: myelin basic protein, glutamate, deimination, astrocytes, inflammation

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39 Effects of Turmeric on Uterine Tissue in Rats with Metabolic Syndrome Induced by High Fructose Diet

Authors: Mesih Kocamuftuoglu, Gonca Ozan, Enver Ozan, Nalan Kaya, Sema Temizer Ozan

Abstract:

Metabolic Syndrome, one of the common metabolic disorder, occurs with co-development of insulin resistance, obesity, dislipidemia and hypertension problems. Insulin resistance appears to play a pathogenic role in the metabolic syndrome. Also, there is a relationship between insulin resistance and infertility as known. Turmeric (Curcuma longa L.) a polyphenolic chemical is widely used for its coloring, flavoring, and medicinal properties, and exhibits a strong antioxidant activity. In this study, we assess the effects of turmeric on rat uterine tissue in metabolic syndrome model induced by high fructose diet. Thirty-two adult female Wistar rats weighing 220±20 g were randomly divided into four groups (n=8) as follows; control, fructose, turmeric, and fructose plus turmeric. Metabolic syndrome was induced by fructose solution 20% (w/v) in tap water, and turmeric (C.Longa) administered at the dose of 80 mg/kg body weight every other day by oral gavage. After the experimental period of 8 weeks, rats were decapitated, serum and uterine tissues were removed. Serum lipid profile, glucose, insülin levels were measured. Uterine tissues were fixed for histological analyzes. The uterine tissue sections were stained with hematoxylin-eosin (H & E) stain, then examined and photographed on a light microscope (Novel N-800Mx20). As a result, fructose consumption effected serum lipids, insulin levels, and insulin resistance significantly. Endometrium and myometrium layers were observed in normal structure in control group of uterine tissues. Perivascular edema, peri glandular fibrosis, and inflammatory cell increase were detected in fructose group. Sections of the fructose plus turmeric group showed a significant improvement in findings when compared to the fructose group. Turmeric group cell structures were observed similar with the control group. These results demonstrated that high-fructose consumption could change the structure of the uterine tissue. On the other hand, turmeric administration has beneficial effects on uterine tissue at that dose and duration when administered with fructose.

Keywords: metabolic syndrome, rat, turmeric, uterus

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38 Effects of Brewer's Yeast Peptide Extract on the Growth of Probiotics and Gut Microbiota

Authors: Manuela Amorim, Cláudia S. Marques, Maria Conceição Calhau, Hélder J. Pinheiro, Maria Manuela Pintado

Abstract:

Recently it has been recognized peptides from different food sources with biological activities. However, no relevant study has proven the potential of brewer yeast peptides in the modulation of gut microbiota. The importance of human intestinal microbiota in maintaining host health is well known. Probiotics, prebiotics and the combination of these two components, can contribute to support an adequate balance of the bacterial population in the human large intestine. The survival of many bacterial species inhabiting the large bowel depends essentially on the substrates made available to them, most of which come directly from the diet. Some of these substrates can be selectively considered as prebiotics, which are food ingredients that can stimulate beneficial bacteria such as Lactobacilli or Bifidobacteria growth in the colon. Moreover, conventional food can be used as vehicle to intake bioactive compounds that provide those health benefits and increase people well-being. In this way, the main objective of this work was to study the potential prebiotic activity of brewer yeast peptide extract (BYP) obtained via hydrolysis of yeast proteins by cardosins present in Cynara cardunculus extract for possible use as a functional ingredient. To evaluate the effect of BYP on the modulation of gut microbiota in diet-induced obesity model, Wistar rats were fed either with a standard or a high-fat diet. Quantified via 16S ribosomal RNA (rRNA) expression by quantitative PCR (qPCR), genera of beneficial bacteria (Lactobacillus spp. and Bifidobacterium spp.) and three main phyla (Firmicutes, Bacteroidetes and Actinobacteria) were assessed. Results showed relative abundance of Lactobacillus spp., Bifidobacterium spp. and Bacteroidetes was significantly increased (P < 0.05) by BYP. Consequently, the potential health-promoting effects of WPE through modulation of gut microbiota were demonstrated in vivo. Altogether, these findings highlight the possible intervention of BYP as gut microbiota enhancer, promoting healthy life style, and the incorporation in new food products, leads them bringing associated benefits endorsing a new trend in the improvement of new value-added food products.

Keywords: functional ingredients, gut microbiota, prebiotics, brewer yeast peptide extract

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37 Synergistic and Antagonistic Interactions between Garlic Extracts and Metformin in Diabetes Treatment

Authors: Ikram Elsiddig, Yacouba Djamila, Amna Hamad

Abstract:

Abstract—The worldwide increasing of using herbs in form of medicine with or without prescription medications potentiates the interactions between herbal products and conventional medicines; due to more research for herb-drug interactions are needed. for a long time hyperglycemia had been treated with several medicinal plants. A. sativum, belonging to the Liliaceae family is well known for its medicinal uses in African traditional medicine, it used for treating of many human diseases mainly diabetes, high cholesterol and high blood pressure. The purpose of this study is to determine the interaction effect between A. sativum bulb extracts and metformin drug used in diabetes treatment. The in vitro and in vivo evaluation were conducted by glucose reuptake using isolated rats hemidiaphgrams tissue and by estimate glucose tolerance in glucose-loaded wistar albino rats. The results showed that, petroleum ether, chloroform and ethyl acetate extracts were found to have activity of glucose uptake in isolated rats hemidiaphgrams of 24.11 mg/g, 19.07 mg/g and 15.66 mg/g compared to metformin drug of 17 mg/g. These activity were reducded to 17.8 mg/g, 13.59 mg/g and 14.46 mg/g after combination with metformin, metformin itself reduced to 13.59 mg/g, 14.46 mg/g and 12.71 mg/g in comination with chloroform and ethyl acetate. These decrease in activity could be due to herbal–drug interaction between the extracts of A. sativum bulb and metformin drug. The interaction between A. sativum extract and metformin was also shown by in vivo study on the induced hyperglycemic rats. The glucose level after administered of 200 mg/kg was found to be increase with 47.2 % and 17.7% at first and second hour compared to the increase of blood glucose in the control group of 82.6% and76.7%.. At fourth hour the glucose level was became less than normal with 3.4% compared to control which continue to increase with 68.2%. Dose of 400 mg/kg at first hour showed increase in blood glucose of 31.5 %, at second and fourth hours the glucose level was became less than normal with decrease of 3.2 % and 30.4%. After combination the activity was found to be less than that of extract at both high and low dose, whereas, at first and second hour, the glucose level was found to be increase with 50.4% and 21.2%, at fourth hour the glucose level was became less than normal with 14%. Therefore A. sativum could be a potential source for anti-diabetic when it used alone, and it is significant important to use the garlic extract alone instead of combined with Metformin drug in diabetes- treatment.

Keywords: Antagonistic, Garlic, Metformin, Synergistic

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36 Comparison of β-Cell Regenerative Potentials of Selected Sri Lankan Medicinal Plant Extracts in Alloxan-Induced Diabetic Rats

Authors: A. P. Attanayake, K. A. P. W. Jayatilaka, L. K. B. Mudduwa, C. Pathirana

Abstract:

Triggering of β-cell regeneration is a recognized therapeutic strategy for the treatment of type 1 diabetes mellitus. One such approach to foster restoration and regeneration of β-cells is from exogenous natural extracts. The aim of the present study was to investigate and compare the β-cell regenerative potentials of the extracts of Spondias pinnata (Linn. f.) Kurz, Coccinia grandis (L.) Voigt and Gmelina arborea Roxb. in alloxan induced diabetic rats. Wistar rats were divided in to six groups (n=6); healthy untreated rats, alloxan induced diabetic untreated rats (150 mg/kg, ip), diabetic rats receiving the extracts of S. pinnata (1.0 g/kg), C. grandis (0.75 g/kg), G. arobrea (1.00 g/kg) and diabetic rats receiving glibenclamide (0.5 mg/kg) for 30 days. The assessment of selected biochemical parameters, histopathology and immunohistochemistry in the pancreatic tissue were done on the 30th day. The reduction in the percentage of HbA1C was in the decreasing order of C. grandis (35%), G. arborea (31%) and S. pinnata (29%) in alloxan induced diabetic rats (p< 0.05). The concentration of serum fructosamine, insulin and C-peptide were decreased significantly in a decreasing order of C. grandis (30%, 72%, 51%), G. arborea (25%, 44%, 44%) and S. pinnata (27%, 34%, 24%) in alloxan induced diabetic rats (p < 0.05). The extent of β-cell regeneration was in the decreasing order of C. grandis, G. arborea, S. pinnata reflected through the increased percentage of insulin secreting β-cells in alloxan induced diabetic rats. The extract of C. grandis produced the highest degree of β-cell regeneration demonstrated through an increase in the number of islets and percentage of the insulin secreting β-cells (75%) in the pancreas of diabetic rats (p < 0.05). Further the C. grandis extract produced a significant increase in mean profile diameter in small (118%), average (10%), and large (13%) islets as compared with diabetic control rats respectively. However, statistically significant increase in the islet profile diameter was shown only in average (2%) and large (5%) islets in the G. arborea extract treated rats and large islets (5%) in S. pinnata extract treated diabetic rats (p < 0.05). The β-cell regeneration potency was in the decreasing order of C. grandis (0.75 g/kg), G. arborea (1.00 g/kg) and S. pinnata (1.00 g/kg) in alloxan induced diabetic rats. The three plant extracts may be useful as natural agents of triggering the β-cell regeneration in the management of type 1 diabetes mellitus.

Keywords: alloxan-induced diabetic rats, β-cell regeneration, histopathology, immunohistochemistry

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35 Effect of Pioglitazone on Intracellular Na+ Homeostasis in Metabolic Syndrome-Induced Cardiomyopathy in Male Rats

Authors: Ayca Bilginoglu, Belma Turan

Abstract:

Metabolic syndrome, is associated impaired blood glucose level, insulin resistance, dyslipidemia caused by abdominal obesity. Also, it is related with cardiovascular risk accumulation and cardiomyopathy. The hypothesis of this study was to examine the effect of thiazolidinediones such as pioglitazone which is widely used insulin-sensitizing agents that improve glycemic control, on intracellular Na+ homeostasis in metabolic syndrome-induced cardiomyopathy in male rats. Male Wistar-Albino rats were randomly divided into three groups, namely control (Con, n=7), metabolic syndrome (MetS, n=7) and pioglitazone treated metabolic syndrome group (MetS+PGZ, n=7). Metabolic syndrome was induced by providing drinking water that was 32% sucrose, for 18 weeks. All of the animals were exposed to a 12 h light – 12 h dark cycle. Abdominal obesity and glucose intolerance had measured as a marker of metabolic syndrome. Intracellular Na+ ([Na+]i) is an important modulator of excitation–contraction coupling in heart. [Na+]i at rest and [Na+]i during pacing with electrical field stimulation in 0.2 Hz, 0.8 Hz, 2.0 Hz stimulation frequency were recorded in cardiomyocytes. Also, Na+ channel current (INa) density and I-V curve were measured to understand [Na+]i homeostasis. In results, high sucrose intake, as well as the normal daily diet, significantly increased body mass and blood glucose level of the rats in the metabolic syndrome group as compared with the non-treated control group. In MetS+PZG group, the blood glucose level and body inclined to decrease to the Con group. There was a decrease in INa density and there was a shift both activation and inactivation curve of INa. Pioglitazone reversed the shift to the control side. Basal [Na+]i either MetS and Con group were not significantly different, but there was a significantly increase in [Na+]i in stimulated cardiomyocytes in MetS group. Furthermore, pioglitazone had not effect on basal [Na+]i but it reversed the increase in [Na+]i in stimulated cardiomyocytes to the that of Con group. Results of the present study suggest that pioglitazone has a significant effect on the Na+ homeostasis in the metabolic syndrome induced cardiomyopathy in rats. All animal procedures and experiments were approved by the Animal Ethics Committee of Ankara University Faculty of Medicine (2015-2-37).

Keywords: insulin resistance, intracellular sodium, metabolic syndrome, sodium current

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