Search results for: old rats
Commenced in January 2007
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Paper Count: 733

Search results for: old rats

403 Physicochemical and Biochemical Characterization of Olea europea Var. Oleaster Oil and Determination of Its Effects on Blood Parameters

Authors: Asma Gherib, Imen Merzougui, Cherifa Henchiri

Abstract:

This present study has allowed to evaluate the physico chemical characteristics, fatty acid composition and the hypolipidemic effect of Oleaster oil Olea europea var. Oleaster, from the area of El Kala, "Eastern Algeria" on rats "Wistar albinos". The physico chemical characteristics: acidity (0,73%), peroxide value (14, 16 meqO2/kg oil) and iodine value (74,08 g iodine/100 g of oil) are consistent with international standards. The dosage of FA revealed a wealth of oil with UFA (76,7%), mainly composed of 65.43% of MUFA whose major fatty acid is oleic acid (63,57%). The experiment on rats receiving a diet rich in saturated fats and hydrogenated oils revealed that the consumption of Oleaster oil at the dose of 10 g and 20 g for 15 and 30 days improves plasma lipid profile by decreasing the rates of TC, TG, TL, and LDL-C with an increase in the rate of HDL-C serum. The importance of these effects depends on the dose and period of treatment.

Keywords: oleaster oil, fatty acid, Olea europea, oleic acid, lipid profile

Procedia PDF Downloads 486
402 The Effect of Lepidium Meyenii on Viability, Motility, and Sperm Morphology in Treatment of Infertility Among Adult Male Wistar Rats

Authors: Arefeh Sabzipour

Abstract:

In the present work, the effect of Lepidium meyenii on viability, motility, and sperm morphology in the treatment of infertility of adult male Wistar rats was evaluated. 21 male Wistar rats were adopted, fed and brought up in the same conditions to reach the weight of 230±5 g. after that, they were randomly divided into three groups, including two experimental groups and one control group, each group consisted of 7 rates. Lepidium meyenii was extracted and pulverized. Mice in the control group were treated with distilled water, and experimental groups were gavage with alcoholic juice extracted from Lepidium meyenii once a day for 10 consecutive days. After rates were killed, the testes were isolated. Different parameters includes semen volume in mice, sperm count, sperm motility, morphology, and viability, were evaluated. The results shows that sperm motility and sperm survival indices were significantly different between groups, and sperm count and sperm morphology indices were not significantly different. Sperm motility index in intervention group 1 was equal to 77.00±2.499 and was significantly higher than the one in intervention group two (70.14±3.579, P=0.018) and control group (69.43 ±7.323, P=0.018). Sperm survival index was 91.14 ± 2.410 in intervention group 1, 79.43± 5.062 in intervention group 2, and 76.71.6.651 in the control group (P<0.001). Based on the results of the present study, Lepidium meyenii had great effect on improving sperm indices of mice, especially sperm motility index and sperm survival index. Sperm count index and sperm morphology index, although increased, were not statistically significant.

Keywords: infertility, lepidium meyenii, sperm morphology, sperm survival

Procedia PDF Downloads 78
401 The Effect of Lepidium Meyenii on Viability, Motility, and Sperm Morphology in Treatment of Infertility Among Adult Male Wistar Rats

Authors: Arefeh Sabzipour

Abstract:

In the present work, the effect of Lepidium meyenii on viability, motility, and sperm morphology in the treatment of infertility of adult male Wistar rats was evaluated. 21 male Wistar rats were adopted, fed and brought up in the same conditions to reach the weight of 230±5 g. after that they were randomly divided into three groups including two experimental groups and one control group, each group consisted of 7 rates. Lepidium meyenii was extracted and pulverized. Mice in the control group were treated with distilled water and experimental groups were gavage with alcoholic juice extracted from Lepidium meyenii once a day for 10 consecutive days. After rates were killed, the testes were isolated. Different parameters includes semen volume in mice, sperm count, sperm motility, morphology, and viability were evaluated. The results shows that sperm motility and sperm survival indices were significantly different between groups and sperm count and sperm morphology indices were not significantly different. Sperm motility index in intervention group 1 was equal to 77.00±2.499 and was significantly higher than the one in intervention group two (70.14±3.579, P=0.018) and control group (69.43 ±7.323, P=0.018). Sperm survival index was 91.14 ± 2.410 in intervention group 1, 79.43± 5.062 in intervention group 2, and 76.71.6.651 in control group (P<0.001). Based on the results of the present study, Lepidium meyenii had great effect on improving sperm indices of mice, especially sperm motility index and sperm survival index. Sperm count index and sperm morphology index, although increased, were not statistically significant.

Keywords: infertility, Lepidium meyenii, sperm morphology, sperm survival

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400 Anti-Hypertensive Effect of Proteolysate Generated from Actinopyga lecanora in Rats

Authors: Mahdokht Sadeghvishkaei, Azizah Abdul-Hamid, Amin Ismail, Nazamid Saari

Abstract:

Hypertension is a common and serious chronic health problem and known as the most important risk factor for development of many diseases such as stroke. Since angiotensin I-converting enzyme (ACE) is the key enzyme involved in blood pressure, one of the well accepted mechanisms to control hypertension is through ACE inhibition. The ACE inhibitory effect of Actinopyga lecanora (stone fish) proteolysate in vitro had been reported. Hence, this study aimed to evaluate the ACE inhibitory potential of Actinopyga lecanora proteolysate in vivo in normotensive rats. Therefore the ACE inhibitory capability of the proteolysate to prevent increasing systolic blood pressure, after inducing hypertension by angiotensin I was examined. The pre-fed rats with the proteolysates at various doses (200, 400, 800 mg/kg body weight) revealed the significant (p ≤ 0.05) suppression effect compared with control groups. Furthermore, different doses of the proteolysate (200, 400, 800 mg/kg body weight) were examined to find its optimum effective dose. Results depicted that 800 mg proteolysate/kg body weight significantly reduced systolic blood pressure without negative effect on normal blood pressure (p ≤ 0.05). Furthermore, Sub-acute toxicity study based on OECD guideline demonstrated the safety of the proteolysate in vivo. The present study indicated that the proteolysate at a dose of 1000 mg/kg daily for 14 days did not cause toxicity signs such as death, changes in activity, or piloerection. Since there are no significant differences between treated groups and control groups, hematological and biochemical analysis confirmed safety of the proteolysate (p > 0.05). In addition, there were no significant differences between organs weights of the treated groups and the control groups. Morphologically, neither histopathological changes, nor gross abnormalities were observed. However, the proteolysate caused significant decrease in body weight in relation to the control groups (p ≤ 0.05) probably due to appetite stimulation by the proteolysate, leading to decreased food consumption in sub-acute group. It is concluded that the proteolysate generated from Actinopyga lecanora possess a significant anti-hypertensive effect and would be potentially used as natural alternative of ACE inhibitors.

Keywords: ACE inhibition, Actinopyga lecanora, anti-hypertensive activity, bioactive peptides, normotensive rats

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399 Aframomum melegueta Improves Antioxidant Status of Type 2 Diabetes Rats Model

Authors: Aminu Mohammed, Shahidul Islam

Abstract:

Aframomum melegueta K.Schum commonly known as Grains of Paradise has been a popularly used spice in most of the African food preparation. Available data have shown that ethyl acetate fraction from crude ethanolic extract exhibited α-amylase and α-glucosidase inhibitory actions, improved pancreatic β-cell damage and ameliorated insulin resistance in diabetic rats. Additionally, 6-gingerol, 6-shogaol, 6-paradol and oleanolic acid are shown to be the compounds responsible for the antidiabetic action of A. melegueta. However, detail antioxidant potential of this spice in a diabetic animal model has not yet been reported. Thus, the present study investigates the effect of oral consumption of A. melegueta fruit on the in vivo antioxidant status of type 2 diabetes (T2D) model of rats. T2D was induced in rats by feeding a 10% fructose solution ad libitum for two weeks followed by a single intraperitoneal injection of streptozotocin (40 mg/kg body weight (bw)). The animals were orally administered with 150 (DAML) or 300 mg/kg bw (DAMH) of the fraction once daily for four weeks. Data were analyzed by using a statistical software package (SPSS for Windows, version 22, IBM Corporation, NY, USA) using Tukey’s-HSD multiple range post-hoc test. Values were considered significantly different at p < 0.05. According to the data, after four weeks of intervention, diabetic untreated animals showed significantly (p < 0.05) elevation of blood glucose levels. The levels of thiobarbituric acid reactive substances (TBARS) were observed to increase with concomitant reduction of reduced glutathione (GSH) levels in the serum and organs (liver, kidney, heart and pancreas) of diabetic untreated animals. The activities of endogenous antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and reductase) were greatly reduced in the serum and organs of diabetic untreated animals compared to the normal animals. These alterations were reverted to near-normal after the treatment of A. melegueta fruit in the treated groups (DAML & DAMH) within the study period, especially at the dose of 300 mg/kg bw. This potent antioxidant action may partly be attributed to the presence of the 6-Gingerol, 6-shogaol and 6-paradol are known to possess antioxidant action. The results of our study showed that A. melegueta intake improved the antioxidant status of T2D rats and therefore could be used to ameliorate the diabetes-induced oxidative damage.

Keywords: Aframomum melegueta, antioxidant, ethyl acetate extract, type 2 diabetes

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398 Isolation and Transplantation of Hepatocytes in an Experimental Model

Authors: Inas Raafat, Azza El Bassiouny, Waldemar L. Olszewsky, Nagui E. Mikhail, Mona Nossier, Nora E. I. El-Bassiouni, Mona Zoheiry, Houda Abou Taleb, Noha Abd El-Aal, Ali Baioumy, Shimaa Attia

Abstract:

Background: Orthotopic liver transplantation is an established treatment for patients with severe acute and end-stage chronic liver disease. The shortage of donor organs continues to be the rate-limiting factor for liver transplantation throughout the world. Hepatocyte transplantation is a promising treatment for several liver diseases and can, also, be used as a "bridge" to liver transplantation in cases of liver failure. Aim of the work: This study was designed to develop a highly efficient protocol for isolation and transplantation of hepatocytes in experimental Lewis rat model to provide satisfactory guidelines for future application on humans.Materials and Methods: Hepatocytes were isolated from the liver by double perfusion technique and bone marrow cells were isolated by centrifugation of shafts of tibia and femur of donor Lewis rats. Recipient rats were subjected to sub-lethal dose of irradiation 2 days before transplantation. In a laparotomy operation the spleen was injected by freshly isolated hepatocytes and bone marrow cells were injected intravenously. The animals were sacrificed 45 day latter and splenic sections were prepared and stained with H & E, PAS AFP and Prox1. Results: The data obtained from this study showed that the double perfusion technique is successful in separation of hepatocytes regarding cell number and viability. Also the method used for bone marrow cells separation gave excellent results regarding cell number and viability. Intrasplenic engraftment of hepatocytes and live tissue formation within the splenic tissue were found in 70% of cases. Hematoxylin and eosin stained splenic sections from 7 rats showed sheets and clusters of cells among the splenic tissues. Periodic Acid Schiff stained splenic sections from 7 rats showed clusters of hepatocytes with intensely stained pink cytoplasmic granules denoting the presence of glycogen. Splenic sections from 7 rats stained with anti-α-fetoprotein antibody showed brownish cytoplasmic staining of the hepatocytes denoting positive expression of AFP. Splenic sections from 7 rats stained with anti-Prox1 showed brownish nuclear staining of the hepatocytes denoting positive expression of Prox1 gene on these cells. Also, positive expression of Prox1 gene was detected on lymphocytes aggregations in the spleens. Conclusions: Isolation of liver cells by double perfusion technique using collagenase buffer is a reliable method that has a very satisfactory yield regarding cell number and viability. The intrasplenic route of transplantation of the freshly isolated liver cells in an immunocompromised model was found to give good results regarding cell engraftment and tissue formation. Further studies are needed to assess function of engrafted hepatocytes by measuring prothrombin time, serum albumin and bilirubin levels.

Keywords: Lewis rats, hepatocytes, BMCs, transplantation, AFP, Prox1

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397 The Evaluation of the Effects of Atypical Antipsychotics on Sperm Quality by Computer-Assisted Sperm Analysis in Rats

Authors: O. Atli Eklioglu

Abstract:

Atypical antipsychotics such as quetiapine, olanzapine, and risperidone have been frequently and chronically used to treat psychiatric disorders accompanied by psychosis mainly schizophrenia. Since these drugs are commonly used in male patients of reproductive age, it is required to determine the possible effects of them on the reproductive system. In this study, it was aimed to evaluate the possible toxic effects of quetiapine, olanzapine and risperidone, which are the most frequently prescribed and chronically used psychiatric drugs, on sperm parameters. For this purpose, quetiapine (10, 20 and 40 mg/kg), olanzapine (2.5, 5 and 10 mg/kg), and risperidone (1.25, 2.5 and 3 mg/kg) were administered to male rats for 28 consecutive days. At the end of this period, sperm concentration, motility, and morphology were investigated by a computer-assisted sperm analysis system. According to the results, sperm parameters were negatively affected by antipsychotic use.

Keywords: quetiapine, olanzapine, risperidone, sperm count, motility, sperm morphology, computer-assisted sperm analysis

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396 Changes in Secretory Products and Lipid Profile in the Epididymis and Spermatozoa of Rats Induced by Aluminium Chloride

Authors: Ramalingam Venugopal, Kalaiselvi Arumugam

Abstract:

Environmental exposure to heavy metals is associated with a wide range of toxic effects. It is evident that heavy metals released in the environment affect the reproductive processes and fertility of animals. Toxic metals affect the male and female reproductive system directly or indirectly. Considering the toxic nature of aluminium and also the major role of secretory products and lipids in sperm maturation, the present study was planned to investigate the effect of aluminium chloride on secretory products like glyceryl phosphoryl choline (GPC), sialic acid, carnitine and acetyl carnitine content and also lipid profiles in the epididymis and spermatozoa of adult rats. Aluminium chloride, 50 mg/kg body weight was administered orally daily for 60 days. 24 hours after the last dose the rats were sacrificed and immediately epididymis was dissected out and spermatozoa was isolated. The weight of the epididymis decreased significantly. GPC and sialic acid content was significantly reduced in the epididymis and not much altered in spermatozoa. Carnitine and acetyl carnitine contents were markedly decreased in the spermatozoa as well as in the epididymis. Aluminium chloride administration caused a marked reduction in total lipid, cholesterol, phospholipids and cholesterol content in epididymis and no significant changes in spermatozoa. Several changes take place in the spermatozoa as they pass through the epididymis. These changes are directly related to the acquisition of fertilizing ability of spermatozoa. From the results, it is evident that aluminium chloride has definite influence on secretory products and lipid profiles in the epididymis. This may eventually have an adverse impact on the fertility of the animal.

Keywords: aluminium chloride, rat, carnitine, GPC, sialic acid, epididymis, spermatozoa

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395 Role of Maternal Astaxanthin Supplementation on Brain Derived Neurotrophic Factor and Spatial Learning Behavior in Wistar Rat Offspring’s

Authors: K. M. Damodara Gowda

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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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394 Therapeutic Efficacy of Clompanus Pubescens Leaves Fractions via Downregulation of Neuronal Cholinesterases/NA⁺-K⁺ ATPase/IL-1 β and Improving the Neurocognitive and Antioxidants Status of Streptozotocin-Induced Diabetic Rats

Authors: Amos Sunday Onikanni, Bashir Lawal, Babatunji Emmanuel Oyinloye, Gomaa Mostafa-Hedeab, Mohammed Alorabi, Simona Cavalu, Augustine O. Olusola, Chih-Hao Wang, Gaber El-Saber Batiha

Abstract:

The increasing global burden of diabetes mellitus has called for the search for a therapeutic alternative that offers better activities and safety than conventional chemotherapy. Herein, we evaluated the neuroprotective and antioxidant properties of different fractions (ethyl acetate, N-butanol and residual aqueous) of Clompanus pubescens leaves in streptozotocin (STZ)-induced diabetic rats. Our results revealed a significant elevation in the levels of blood glucose, pro-inflammatory cytokines, lipid peroxidation, neuronal activities of acetylcholinesterase, butyrylcholinesterase, nitric oxide, epinephrine, norepinephrine, and Na+/K+-ATPase in diabetic non treated rats. In addition, decreased levels of enzymatic and non-enzymatic antioxidants were observed. Treatment with different fractions of C. pubescens leaves resulted in a significant reversal of the biochemical alteration and improved the neurocognitive deficit in STZ-induced diabetic rats. However, the ethyl-acetate fraction demonstrated higher activities than the other fractions and was characterized for its phytoconstituents, revealing the presence of Gallic acid (713.00 ppm), catechin (0.91 ppm), ferulic acid (0.98 ppm), rutin (59.82 ppm), quercetin (3.22 ppm) and kaempferol (4.07 ppm). Our molecular docking analysis revealed that these compounds exhibited different binding affinities and potentials for targeting BChE/AChE/ IL-1 β/Na+-K+-ATPase. However, only Kampferol and ferulic exhibited good drug-like, ADMET, and permeability properties suitable for use as a neuronal drug target agent. Hence, the ethyl-acetate fraction of C. pubescent leaves could be considered a source of promising bioactive metabolite for the treatment and management of cognitive impairments related to type II diabetes mellitus.

Keywords: diabetes mellitus, neuroprotective, antioxidant, pro-inflammatory cytokines

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393 Effect of Nicorandil, Bone Marrow-Derived Mesenchymal Stem Cells and Their Combination in Isoproterenol-Induced Heart Failure in Rats

Authors: Sarah Elsayed Mohammed, Lamiaa Ahmed Ahmed, Mahmoud Mohammed Khattab

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Aim: The aim of the present study was to investigate whether combined nicorandil and bone marrow-derived mesenchymal stem cells (BMDMSC) treatment could offer an additional benefit in ameliorating isoproterenol (ISO)-induced heart failure in rats. Methods: ISO (85 and 170 mg/kg/day) was injected subcutaneously for 2 successive days, respectively. By day 3, electrocardiographic changes were recorded and serum was separated for determination of CK-MB level for confirmation of myocardial damage. Nicorandil (3 mg/kg/day) was then given orally with or without a single i.v. BMDMSC administration. Electrocardiography and echocardiography were recorded 2 weeks after beginning of treatment. Rats were then sacrificed and ventricles were isolated for estimation of vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) contents, caspase-3 activity as well as inducible nitric oxide synthase (iNOS) and connexin-43 protein expressions. Moreover, histological analysis of myocardial fibrosis was performed and cryosections were done for estimation of homing of BMDMSC. Results: ISO induced a significant increase in ventricles/body weight ratio, left ventricular end diastolic (LVEDD) and systolic dimensions (LVESD), ST segment and QRS duration. Moreover, myocardial fibrosis as well as VEGF, TNF-α and TGF-β contents were significantly increased. On the other hand, connexin-43 protein expression was significantly decreased, while caspase-3 and iNOS protein expressions were significantly increased. Combined therapy provided additional improvement compared to cell treatment alone towards reducing cardiac hypertrophy, fibrosis and inflammation. Furthermore, combined therapy induced significant increase in angiogenesis and BMDMSC homing and prevented ISO induced changes in iNOS, connexin-43 and caspase-3 protein expressions. Conclusion: Combined nicorandil/BMDMSC treatment was superior to BMDMSC alone towards preventing ISO-induced heart failure in rats.

Keywords: fibrosis, isoproterenol, mesenchymal stem cells, nicorandil

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392 Expression of Fibrogenesis Markers after Mesenchymal Stem Cells Therapy for Experimental Liver Cirrhosis

Authors: Tatsiana Ihnatovich, Darya Nizheharodava, Mikalai Halabarodzka, Tatsiana Savitskaya, Marina Zafranskaya

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Liver fibrosis is a complex of histological changes resulting from chronic liver disease accompanied by an excessive production and deposition of extracellular matrix components in the hepatic parenchyma. Liver fibrosis is a serious medical and social problem. Hepatic stellate cells (HSCs) make a significant contribution to the extracellular matrix deposition due to liver injury. Mesenchymal stem cells (MSCs) have a pronounced anti-inflammatory, regenerative and immunomodulatory effect; they are able to differentiate into hepatocytes and induce apoptosis of activated HSCs that opens the prospect of their use for preventing the excessive fibro-formation and the development of liver cirrhosis. The aim of the study is to evaluate the effect of MSCs therapy on the expression of fibrogenesis markers genes in liver tissue and HSCs cultures of rats with experimental liver cirrhosis (ELC). Materials and methods: ELC was induced by the common bile duct ligation (CBDL) in female Wistar rats (n = 19) with an average body weight of 250 (220 ÷ 270) g. Animals from the control group (n = 10) were sham-operated. On the 56th day after the CBDL, the rats of the experimental (n = 12) and the control (n = 5) groups received intraportal MSCs in concentration of 1×106 cells/animal (previously obtained from rat’s bone marrow) or saline, respectively. The animals were taken out of the experiment on the 21st day. HSCs were isolated by sequential liver perfusion in situ with following disaggregation, enzymatic treatment and centrifugation of cell suspension on a two-stage density gradient. The expression of collagen type I (Col1a1) and type III (Col3a1), matrix metalloproteinase type 2 (MMP2) and type 9 (MMP9), tissue inhibitor of matrix metalloproteinases type 1 (TIMP1), transforming growth factor β type 1 (TGFβ1) and type 3 (TGFβ3) was determined by real-time polymerase chain reaction. Statistical analysis was performed using Statistica 10.0. Results: In ELC rats compared to sham-operated animals, a significant increase of all studied markers expression was observed. The administration of MSCs led to a significant decrease of all detectable markers in the experimental group compared to rats without cell therapy. In ELC rats, an increased MMP9/TIMP1 ratio after cell therapy was also detected. The infusion of MSCs in the sham-operated animals did not lead to any changes. In the HSCs from ELC animals, the expression of Col1a1 and Col3a1 exceeded the similar parameters of the control group (p <0.05) and statistically decreased after the MSCs administration. The correlation between Col3a1 (Rs = 0.51, p <0.05), TGFβ1 (Rs = 0.6, p <0.01), and TGFβ3 (Rs = 0.75, p <0.001) expression in HSCs cultures and liver tissue has been found. Conclusion: Intraportal administration of MSCs to rats with ELC leads to a decreased Col1a1 and Col3a1, MMP2 and MMP9, TIMP1, TGFβ1 and TGFβ3 expression. The correlation between the expression of Col3a1, TGFβ1 and TGFβ3 in liver tissue and in HSCs cultures indicates the involvement of activated HSCs in the fibrogenesis that allows considering HSCs to be the main cell therapy target in ELC.

Keywords: cell therapy, experimental liver cirrhosis, hepatic stellate cells, mesenchymal stem cells

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391 Anti-Hyperglycemic Effects and Chemical Analysis of Allium sativum Bulbs Growing in Sudan

Authors: Ikram Mohamed Eltayeb Elsiddig, Yacouba Amina Djamila, Amna El Hassan Hamad

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Hyperglycemia and diabetes have been treated with several medicinal plants for a long time, meanwhile reduce associated side effects than the synthetic ones. Therefore, the search for more effective and safer anti-diabetic agents derived from plants has become an interest area of active research. 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 present study was carried out to investigate the anti-hyperglycemic effect of the extracts of A. sativum bulb growing in Sudan on glucose-loaded Wistar albino rats. A. sativum bulbs were collected from local vegetable market at Khourtoum/ Sudan in a fresh form, identified and authenticated by taxonomist, then dried, and extracted with solvents of increasing polarity: petroleum ether, chloroform, ethyl acetate and methanol by using Soxhlet apparatus. The effect of the extracts on glucose uptake was evaluated by using the isolated rats hemidiaphgrams after loading the fasting rats with glucose, and the anti-hyperglycemic effect was investigated on glucose-loaded Wistar albino rats. Their effects were compared to control rats administered with the vehicle and to a standard group administered with Metformin standard drug. The most active extract was analyzed chemically using GC-MS analysis compared to NIST library. The results showed significant anti-diabetic effect of extracts of A. sativum bulb growing in Sudan. Addition to the hypoglycemic activity of A. sativum extracts was found to be decreased with increase in the polarity of the extraction solvent; this may explain the less polarity of substance responsible for the activity and their concentration decreased with polarity increase. The petroleum ether extract possess anti-hyperglycemic activity more significant than the other extracts and the Metformin standard drug with p-value 0.000** of 400mg/kg at 1 hour, 2 hour and four hour; and p-value 0.019*, 0.015* and 0.010* of 200mg/kg at 1 hour, 2 hour and four hour respectively. The GC-MS analysis of petroleum ether extract, with highest anti -diabetes activity showed the presence of Methyl linolate (42.75%), Hexadecanoic acid, methyl ester (10.54%), Methyl α-linolenate (8.36%), Dotriacontane (6.83), Tetrapentacontane (6.33), Methyl 18-methylnonadecanoate (4.8), Phenol,2,2’-methylenebis[6-(1,1-dimethylethyl)-4-methyl] (3.25), Methyl 20-methyl-heneicosanoate (2.70), Pentatriacontane (2.13) and many other minor compounds. The most of these compounds are well known for their anti-diabetic activity. The study concluded that A. sativum bulbs extracts were found to enhanced the reuptake of glucose in the isolated rat hemidiaphragm and have antihyperglycemic effect when evaluated on glucose-loaded albino rats with petroleum ether extract activity more significant than the Metformin standard drug.

Keywords: Allium, anti-hyperglycemic, bulbs, sativum

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390 Protective Approach of Mentha Piperita against Cadmium Induced Renotoxicity in Albino Rats

Authors: Baby Tabassum, Priya Bajaj

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Cadmium is the second most hazardous heavy metal occurring in both elemental as well as compound forms. It is a highly toxic metal with a very high bio-concentration factor (BCF>100). WHO permitted groundwater cadmium concentration is 0.005 mg/L only, but reality is far away from this limit. A number of natural and anthropogenic industrial activities contribute to the spread of cadmium into the environment. The present study had been designated to find out the renal changes at functional level after cadmium intoxication and protection against these changes offered by Mentha piperata. For the purpose, albino rats were selected as the model organism. Cadmium significantly increases the serum level of serum proteins and nitrogenous wastes showing reduced filtration rate of kidneys. Pretreatment with Mentha piperata leaf extract causes significant retention of these levels to normalcy. These findings conclude that Cadmium exposure affects renal functioning but Mentha could prevent it, proving its nephro-protective potential against heavy metal toxicity.

Keywords: albino rat, cadmium, Mentha piperata, nephrotoxicity

Procedia PDF Downloads 397
389 Carbendazim Toxicity and Ameliorative Effect of Vitamin E in African Giant Rats

Authors: A. O. Omonona, T. A. Jarikre

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Increase specialization in agriculture and use of pesticides may inadvertently cause ecosystem degradation and eventually loss of biodiversity. The populations of numerous wildlife species have undergone a precipitous decline. Many of these problems have been attributed directly to habitat loss and over exploitation resulting from unregulated pesticide uses. Carbendazim a broad spectrum benzimidazole fungicide and a metabolite of benomyl, is used to control plant disease in cereals and fruit. The effect of carbendazim exposure and the ameliorative effect of tocopherol (vitamin E) were assessed on African giant rat AGR. Hematological, biochemical and histological changes were used to determine the health condition of the animals exposed to pesticide. Sixteen AGR were stabilized, weighed and then divided into four experimental groups (A to D). Two groups were pretreated with vitamin. Group A was exposed to carbendazim only, B- carbendazim + vitamin, C- vitamin only, and D- blank (control). Packed cell volume PCV was estimated by the microhematocrit method, Leucocyte and Platelet counts were determined using the hemocytometric method. Cholinesterase (AchE) and markers of oxidative stress were quantified, and tissue changes examined microscopically. There were no behavioral changes observed in the animals, but there was a decrease in body weight and abortion after 23 days of exposure to carbendazim. There was significant differences in the packed cell volume, the hemoglobin concentration and the red blood cell counts (p < 0.05). The increases in malonyl aldehyde MDA was significant (p < 0.05) in the pesticide intoxicated rats compared to control. Vitamin E supplementation reduced MDA level significantly (p < 0.05). There was a sharp remarkable decrease in acetylcholinesterase levels in the pesticide intoxicated rats (p < 0.05). Vitamin E supplementation normalise the AchE levels comparable to that in control. Grossly, the vital organs appeared normal in the pesticide exposed and control groups except moderate pulmonary congestion. Microscopically, there was severe diffuse hepatocellular swelling in carbendazim exposed group. The severity of hepatocellular injury was reduced in the rats with vitamin E. This study ascertained the toxic effect of carbendazim and antioxidative properties of vitamins in the Africa giant rat.

Keywords: African giant rat, antioxidant, carbendazim, pesticides, toxicity

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388 Effect of 8-OH-DPAT on the Behavioral Indicators of Stress and on the Number of Astrocytes after Exposure to Chronic Stress

Authors: Ivette Gonzalez-Rivera, Diana B. Paz-Trejo, Oscar Galicia-Castillo, David N. Velazquez-Martinez, Hugo Sanchez-Castillo

Abstract:

Prolonged exposure to stress can cause disorders related with dysfunction in the prefrontal cortex such as generalized anxiety and depression. These disorders involve alterations in neurotransmitter systems; the serotonergic system—a target of the drugs that are commonly used as a treatment to these disorders—is one of them. Recent studies suggest that 5-HT1A receptors play a pivotal role in the serotonergic system regulation and in stress responses. In the same way, there is increasing evidence that astrocytes are involved in the pathophysiology of stress. The aim of this study was to examine the effects of 8-OH-DPAT, a selective agonist of 5-HT1A receptors, in the behavioral signs of anxiety and anhedonia as well as in the number of astrocytes in the medial prefrontal cortex (mPFC) after exposure to chronic stress. They used 50 male Wistar rats of 250-350 grams housed in standard laboratory conditions and treated in accordance with the ethical standards of use and care of laboratory animals. A protocol of chronic unpredictable stress was used for 10 consecutive days during which the presentation of stressors such as motion restriction, water deprivation, wet bed, among others, were used. 40 rats were subjected to the stress protocol and then were divided into 4 groups of 10 rats each, which were administered 8-OH-DPAT (Tocris, USA) intraperitoneally with saline as vehicle in doses 0.0, 0.3, 1.0 and 2.0 mg/kg respectively. Another 10 rats were not subjected to the stress protocol or the drug. Subsequently, all the rats were measured in an open field test, a forced swimming test, sucrose consume, and a cero maze test. At the end of this procedure, the animals were sacrificed, the brain was removed and the tissue of the mPFC (Bregma: 4.20, 3.70, 2.70, 2.20) was processed in immunofluorescence staining for astrocytes (Anti-GFAP antibody - astrocyte maker, ABCAM). Statistically significant differences were found in the behavioral tests of all groups, showing that the stress group with saline administration had more indicators of anxiety and anhedonia than the control group and the groups with administration of 8-OH-DPAT. Also, a dose dependent effect of 8-OH-DPAT was found on the number of astrocytes in the mPFC. The results show that 8-OH-DPAT can modulate the effect of stress in both behavioral and anatomical level. Also they indicate that 5-HT1A receptors and astrocytes play an important role in the stress response and may modulate the therapeutic effect of serotonergic drugs, so they should be explored as a fundamental part in the treatment of symptoms of stress and in the understanding of the mechanisms of stress responses.

Keywords: anxiety, prefrontal cortex, serotonergic system, stress

Procedia PDF Downloads 323
387 Cardiac Protective Effect of Olive Oil against Ischemia Reperfusion- Induced Cardiac Arrhythmias in Isolated Diabetic Rat Hearts

Authors: Ishfaq A. Bukhari, Bassem Yousef Sheikh, Abdulrahman Almotrefi, Osama Yousaf, Amer Mahmood

Abstract:

Olive oil is the primary source of fat in the Mediterranean diet which is associated with a low mortality for cardiovascular disease. Olive oil is rich in monounsaturated fatty acids, and has been reported for variety of beneficial cardiovascular effects including blood pressure lowering, anti-platelet, anti-diabetic and anti-inflammatory effects. Growing number evidences from preclinical and clinical studies have shown that olive oil improves insulin resistance, decrease vessels stiffness and prevent thromboembolism. We evaluated the effects of olive against streptozotocin-induced physiological disorders in the animal models of diabetes and ischemia and reperfusion (I/R)- induced cardiac arrhythmias. Diabetes was induced in male rats with a single intraperitoneal injection of streptozotocin (60 mg/kg), rats were treated for two months with olive oil (1 ml/kg p.o). Control animals received saline. Blood glucose, body weight were monitored every 14 days. At the end of the treatment rats were sacrificed hearts were isolated for mounting on langedorff’s apparatus. The blood glucose and body weight was not significantly different in the control and olive treated animals. The control diabetic animals exhibited 100% incidence of I/R –induced ventricular fibrillation which was reduced to 0% with olive oil, treatment. The duration of ventricular fibrillation reduced from 98.8± 2.3 (control) to 0 seconds in the olive oil treated group. Diltiazem, a calcium channel blocker (1 µm/L) showed similar results and protected the I/R-induced cardiac disorders. The biochemical analysis of the cardiac tissues showed that diabetes and I/R produce marked pathological changes in the cardiomyocytes including decreased glutathione (GSH) and increased oxidative stress (Malondialdehyde; MDA). Pretreatment of animals with olive oil (1 ml/kg p.o) increased GSH and MDA levels. Olive oil also improved the diabetic-induced histopathological changes in the cardiomyocytes. These finding indicates that olive possesses cardiac protective properties. Further studies are under way in our lab to explore the mechanism of the cardio-protective effect of olive oil.

Keywords: diabeties, ischemia-reperfusion, olive oil, rats heart

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386 Osteoprotective Effect of Lawsonia inermis

Authors: Suraj Muke, Vikas Mankumare, Sadhana Sathaye

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Osteoporosis is the most common metabolic bone disease which affects an estimated 25 million people worldwide, leading to 1 million fractures, 40,000 annual deaths and health costs of billions of dollars. It is estimated that about 80% of total osteoporosis patients are women, amongst which majority are above the age of 45 years. Postmenopausal osteoporosis is associated with lack of intestinal calcium absorption, increasing pro-oxidant and inflammatory mediators. Lawsonia inermis is a biennial dicotyledonous herbaceous shrub is reported to possess a high flavonoid, high phenolic and Inhibitors of osteoclastogenesis like Daphneside and Daphnorin. The present study aimed to screen osteoprotective effect of methanolic extract of Lawsonia inermis (LIM) in rat model along with its antioxidant activity. LIM shows phenolic content 146.3Milligrams of Gallic acid equivalent present per gram of extract and 19.8 Milligrams of rutin per gram of extract of Total flavonoid content with IC50 value 42.99μg/ml. bilateral ovariectomized rat model in which Healthy female wistar rats were used for screening. Treatment with LIM was carried out using graded doses of 25mg/kg, 50mg/kg and 100mg/kg for period of 28 days. The negative control group comprised of ovariectomized rats along with saline treatment for four weeks whereas sham operated rats were used as positive control.LIM showed a decrease in bone turnover by preventing loss of urinary calcium and phosphorous moreover it decreased the alkaline phosphatase levels and loss of bone density is prevented by LIM suggesting decrease in osteoclast activity.

Keywords: antioxidant, osteoclast, osteoporosis, ovariectomized

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385 The Effect of Low and High Dose Curcumin Supplementation on Prevention and Treatment of Sarcopenia: The Concept of Hormesis

Authors: Sevana Daneghian, Leila Chodari, Sahar Mehranfar, Shadi Mohammadpour-Asl, Diman Mahdi

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Sarcopenia is an age-related muscle disease. Lack of antioxidant protection, and cumulative oxidative damage to skeletal muscle are recognized mechanisms. Curcumin is a hormetin as it has a stimulating effect in low doses and an inhibitory effect in high doses. The purpose of this study was to examine the effects of four weeks of curcumin supplementation in presarcopenic and sarcopenic rats, and likelihood of potential negative effects while co-exist with sarcopenia. The rats were divided into 7 groups: young sham rats, 18 months old; presarcopenic control, supplemented with 400 and 1500 mg/kg/day, 24 months old; Sarcopenia control, sarcopenia supplemented with 400 and 1500 mg/kg/day. MDA levels were significantly reduced in the low-dose pre-sarcopenic group compared to the control group. Compared to the corresponding control groups, SOD levels decreased in the groups treated with low-dose presarcopenic supplementation and increased in the high-dose sarcopenic supplemented. GPx levels increased at both doses only in the sarcopenic group compared to the control group. SIRT-1 only increased at low doses in the sarcopenic groups and PGC-1α in both pre-sarcopenia groups compared to the corresponding control. IGF-1 increased compared to the control group at both doses in the pre-sarcopenic group and at high doses in sarcopenic group. Considering the hormetic effects of curcumin, it can be argued that, curcumin supplementation has some positive effects not only at low but also at high doses in both groups. This means that the high doses of curcumin have no negative synergistic effects in addition to oxidative stress during sarcopenia and high-dose supplementation in patients already suffering from high oxidative stress due to sarcopenia is safe and could be considered hormetic.

Keywords: curcumin, hormesis, sarcopenia, muscular atrophy, PGC protein, Sirtuins

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384 Efficacy of Ethanolic Extract of Aerva javanica Aerial Parts in the Amelioration of CCl4-Induced Hepatotoxicity and Oxidative Damage in Rats

Authors: Mohammad K. Parvez, Ahmed H. Arbab, Mohammed S. Al-Dosari, Adnan J. Al-Rehaily

Abstract:

We investigated ex vivo and in vivo antioxidative and hepatoprotective effect of Aerva javanica. Total ethanol extract of A. javanica aerial parts was prepared, and tested on DCFH-toxicated HepG2 cell in CCl4-injured Wistar rats. MTT-assay was used to determine cell viability, and serum biochemical markers of liver injury as well as histopathology were performed. In vitro DPPH and β-carotene free-radical scavenging assay and phytochemical screening of the extract was done. Furthermore, A. javanica total extract was standardized and validated by HPTLC method. While DCFH-injured cells were recovered to about 56.7% by 100 microg/ml of the extract, a 200 microg/ml dose resulted in hepatocytes recovery by about 90.2%. Oral administration of the extract (100 and 200 mg/kg.bw/day) significantly normalized the serum SGOT, SGPT, GGT, ALP, bilirubin, cholesterol, HDL, LDL, VLDL, TG and MDA levels, including tissue NP-SH and TP in CCl4-injured rats. In addition, the histopathology of dissected liver also revealed that A. javanica cured the tissue lesion compared to reference drug, Silymarin. In vitro assays revealed strong free-radical scavenging ability of the extract and presence of alkaloids, flavonoids, tannins, sterols and saponins where Rutin, a well-known antioxidant flavonoid was identified. Our finding therefore, suggests the therapeutic potential of A. javanica in various liver diseases. However, isolation of the active principles, their mechanism of action and other therapeutic contribution remain to be addressed.

Keywords: Aerva javanica, antioxidant, hepatoprotection, rutin

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383 Evaluation of Serine and Branched Chain Amino Acid Levels in Depression and the Beneficial Effects of Exercise in Rats

Authors: V. A. Doss, R. Sowndarya, K. Juila Rose Mary

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Objective: Amino acid neurotransmitter system dysfunction plays a major role in the pathophysiology of depression. The objective of the present study was to identify the amino acids as possible metabolite biomarkers for depression using GCMS (Gas Chromatography Mass Spectrometry) before and after exercise regimen in brain samples of depression induced animal models. Methods: Depression-like behaviour was induced by Chronic Unpredictable mild stress (CUMS). Severity of depression was measured by forced swim test (FST) and sucrose consumption test (SCT). Swimming protocol was followed for 4 weeks of exercise treatment. Brain obtained from depressed and exercise treated rats were used for the metabolite analysis by GCMS. Subsequent statistical analysis obtained by ANOVA followed by post hoc test revealed significant metabolic changes. Results: Amino acids such as alanine, glycine, serine, glutamate, homocysteine, proline and branched chain aminoacids (BCAs) Leucine, Isoleucine, Valine were determined in brain samples of control, depressed and exercised groups. Among these amino acids, the levels of D-Serine and branched chain amino acids were found to be decreased in depression induced rats. After four weeks of swimming exercise regimen, there were improvements in the levels of serine and Branched chain amino acids. Conclusion: We suggest that Serine and BCAs may be investigated as potential metabolite markers using GCMS and their beneficial metabolic changes in Exercise.

Keywords: metabolomics, depression, forced swim test, exercise, amino acid metabolites, GCMS, biomarker

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

Authors: Ikram Elsiddig, Yacouba Djamila, Amna Hamad

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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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381 Neuroprotective Effects of Dehydroepiandrosterone (DHEA) in Rat Model of Alzheimer’s Disease

Authors: Hanan F. Aly, Fateheya M. Metwally, Hanaa H. Ahmed

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The current study is undertaken to elucidate a possible neuroprotective role of dehydroepiandrosterone (DHEA) against the development of Alzheimer’s disease in experimental rat model. Alzheimer’s disease was produced in young female ovariectomized rats by intraperitoneal administration of AlCl3 (4.2 mg/kg body weight) daily for 12 weeks. Half of these animals also received orally DHEA (250 mg/kg body weight, three times weekly) for 18 weeks. Control groups of animals received either DHAE alone, or no DHEA, or were not ovariectomized. After such treatment the animals were analyzed for oxidative stress biomarkers such as hydrogen peroxide, nitric oxide and malondialdehyde, total antioxidant capacity, reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase activities, antiapoptotic marker Bcl-2 and brain derived neurotrophic factor. Also, brain cholinergic markers (acetylcholinesterase and acetylcholine) were determined. The results revealed significant increase in oxidative stress parameters associated with significant decrease in the antioxidant enzyme activities in Al-intoxicated ovariectomized rats. Significant depletion in brain Bcl-2 and brain-derived neurotrophic factor levels were also detected. Moreover, significant elevations in brain acetylcholinesterase activity accompanied with significant reduction in acetylcholine level were recorded. Significant amelioration in all investigated parameters was detected as a result of treatment of Al-intoxicated ovariectomized rats with DHEA. These results were confirmed by histological examination of brain sections. These results clearly indicate a neuroprotective effect of DHEA against Alzheimer’s disease.

Keywords: Alzheimer’s disease, oxidative stress, apoptosis, dehydroepiandrosterone

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380 The Effect of Jujube Extract and Resistance Training on the Reduction of Complications Caused by the Induction of Anabolic Steroid Boldenone on the Histopathological Changes of Pancreatic Tissue of Male Wistar Rats

Authors: Sayyed-javad Ziaolhagh, Ali-Reza Saadatifar

Abstract:

Introduction: Athletes frequently perform anabolic steroid resistance exercise, but the effects of medical doses and abuse along with resistance exercise on structural damage to the Pancreases and also jujube extract are unknown. The aim of this study was to investigate the effects of resistance training on body weight and hip fractures induced by boldenone injection in male rats. Materials and methods: In this experimental study, 30 male Wistar rats aged 8-12 weeks (weight 202±9.34 g) were randomly divided into five groups: control, boldenone, extract of iujuba+boldenone, boldenone+resistance training and boldenone+resistance training +extract of jujuba. The resistance training program included climbing the ladder for 8 weeks, 3 days a week, 1 session training in a day and each session consisted of the 3 sets and 5 repetitions. Injection was conducted in depth in the hamstring once a week on an appointed day. After anesthesia, autopsy was performed, and the cardiac tissue was isolated. Results: Results showed that boldenone caused tissue damage, congestion, and nuclei unclear and diffuse. In the group "resistance + Boldenone," The Pancreases tissue showed a high degree of hyperemia, and the muscle cells were somewhat abnormal. In boldenone + jujube, the appearance of the tissue was normal, and the rejuvenating effect was visible. Conclusion: Boldenone appears to cause structural damage to the Pancreases tissue. Strength training with Jujube Extract can reduce part of the pancreatic system disorders (necrosis and inflammation) caused by anabolic steroid use.

Keywords: boldenone, Jujube extract, pancreases tissue, resistance training

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379 Evaluating the Hepato-Protective Activities of Combination of Aqueous Extract of Roots of Tinospora cordifolia and Rhizomes of Curcuma longa against Paracetamol Induced Hepatic Damage in Rats

Authors: Amberkar Mohanbabu Vittalrao, Avin, Meena Kumari Kamalkishore, Padmanabha Udupa, Vinaykumar Bavimane, Honnegouda

Abstract:

Objective: To evaluate the hepato-protective activity of Tinospora cordiofolia (Tc) against paracetamol induced hepatic damage in rats. Methods: The plant stem (test drug) was procured locally, shade dried, powdered and extracted with water. Silymarin was used as standard hepatoprotective drugs and 2% gum acacia as a control (vehicle) against paracetamol (PCT) induced hepatotoxicity. Results and Discussion: The hepato-protective activity of aqueous stem extract was assessed by paracetamol induced hepatotoxicity preventive model in rats. Alteration in the levels of biochemical markers of hepatic damage like AST, ALT, ALP and lipid peroxides were tested in both paracetamol treated and untreated groups. Paracetamol (3g/kg) had enhanced the AST, ALT, ALP and the lipid peroxides in the serum. Treatment of silymarin and aqueous stem extract of Tc (200 and 400mg/kg) extract showed significant hepatoprotective activity by altering biochemical marker levels to the near normal. Preliminary phytochemical tests were done. Aqueous Tc extract showed presence of phenolic compound and flavonoids. Our findings suggested that Tc extract possessed hepatoprotective activity in a dose dependent manner. Conclusions: Tc was found to possess significant hepatoprotective property when treated with PCT. This was evident by decreasing the liver enzymes significantly when treated with PCT as compared to PCT only treated group (P < 0.05). Hence Tinospora cardiofolia could be a good, promising, preventive agent against PCT induced hepatotoxicity.

Keywords: Tinospora cardiofolia, hepatoprotection, paracetamol, silymarin

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378 Protective Effect of the Histamine H3 Receptor Antagonist DL77 in Behavioral Cognitive Deficits Associated with Schizophrenia

Authors: B. Sadek, N. Khan, D. Łażewska, K. Kieć-Kononowicz

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The effects of the non-imidazole histamine H3 receptor (H3R) antagonist DL77 in passive avoidance paradigm (PAP) and novel object recognition (NOR) task in MK801-induced cognitive deficits associated with schizophrenia (CDS) in adult male rats, and applying donepezil (DOZ) as a reference drug were investigated. The results show that acute systemic administration of DL77 (2.5, 5, and 10 mg/kg, i.p.) significantly improved MK801-induced (0.1 mg/kg, i.p.) memory deficits in PAP. The ameliorating activity of DL77 (5 mg/kg, i.p.) in MK801-induced deficits was partly reversed when rats were pretreated with the centrally-acting H2R antagonist zolantidine (ZOL, 10 mg/kg, i.p.) or with the antimuscarinic antagonist scopolamine (SCO, 0.1 mg/kg, i.p.), but not with the CNS penetrant H1R antagonist pyrilamine (PYR, 10 mg/kg, i.p.). Moreover, the memory enhancing effect of DL77 (5 mg/kg, i.p.) in MK801-induced memory deficits in PAP was strongly reversed when rats were pretreated with a combination of ZOL (10 mg/kg, i.p.) and SCO (1.0 mg/kg, i.p.). Furthermore, the significant ameliorative effect of DL77 (5 mg/kg, i.p.) on MK801-induced long-term memory (LTM) impairment in NOR test was comparable to the DOZ-provided memory-enhancing effect, and was abrogated when animals were pretreated with the histamine H3R agonist R-(α)-methylhistamine (RAMH, 10 mg/kg, i.p.). However, DL77(5 mg/kg, i.p.) failed to provide procognitive effect on MK801-induced short-term memory (STM) impairment in NOR test. In addition, DL77 (5 mg/kg) did not alter anxiety levels and locomotor activity of animals naive to elevated-plus maze (EPM), demonstrating that improved performances with DL77 (5 mg/kg) in PAP or NOR are unrelated to changes in emotional responding or spontaneous locomotor activity. These results provide evidence for the potential of H3Rs for the treatment of neurodegenerative disorders related to impaired memory function, e.g. CDS.

Keywords: histamine H3 receptor, antagonist, learning, memory impairment, passive avoidance paradigm, novel object recognition

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377 Lipid Emulsion versus DigiFab in a Rat Model of Acute Digoxin Toxicity

Authors: Cansu Arslan Turan, Tuba Cimilli Ozturk, Ebru Unal Akoglu, Kemal Aygun, Ecem Deniz Kırkpantur, Ozge Ecmel Onur

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Although the mechanism of action is not well known, Intravenous Lipid Emulsion (ILE) has been shown to be effective in the treatment of lipophilic drug intoxications. It is thought that ILE probably separate the lipophilic drugs from target tissue by creating a lipid-rich compartment in the plasma. The second theory is that ILE provides energy to myocardium with high dose free fatty acids activating the voltage gated calcium channels in the myocytes. In this study, the effects of ILE treatment on digoxin overdose which are frequently observed in emergency departments was searched in an animal model in terms of cardiac side effects and survival. The study was carried out at Yeditepe University, Faculty of Medicine-Experimental Animals Research Center Labs in December 2015. 40 Sprague-Dawley rats weighing 300-400 g were divided into 5 groups randomly. As the pre-treatment, the first group received saline, the second group received lipid, the third group received DigiFab, and the fourth group received DigiFab and lipid. Following that, digoxin was infused to all groups until death except the control group. First arrhythmia and cardiac arrest occurrence times were recorded. As no medication causing arrhythmia was infused, Group 5 was excluded from the statistical analysis performed for the comparisons of first arrhythmia and death time. According to the results although there was no significant difference in the statistical analysis comparing the four groups, as the rats, only exposed to digoxin intoxication were compared with the rats pre-treated with ILE in terms of first arrhythmia time and cardiac arrest occurrence times, significant difference was observed between the groups. According to our results, using DigiFab treatment, intralipid treatment, intralipid and DigiFab treatment for the rats exposed to digoxin intoxication makes no significant difference in terms of the first arrhythmia and death occurrence time. However, it is not possible to say that at the doses we use in the study, ILE treatment might be successful at least as a known antidote. The fact that the statistical significance between the two groups is not observed in the inter-comparisons of all the groups, the study should be repeated in the larger groups.

Keywords: arrhytmia, cardiac arrest, DigiFab, digoxin intoxication

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376 Study of the Protective Effects of Summer Savory against Multiple Organ Damage Induced by Lead Acetate in Rats

Authors: Bassant M. M. Ibrahim, Doha H. Abou Baker, Ahmed Abd Elghafour

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Excessive exposure to heavy metals contributes to the occurrence of deleterious health problems that affect vital organs like the brain, liver, kidneys, and heart. The use of natural products that have antioxidant capabilities may contribute to the protection of these organs. In the present study, the essential oil of summer savory (Satureja hortensis) was used to evaluate its protective effects against lead acetate induced damaging effect on rats’ vital organs, due to its high contents of carvacrol, y-terpinene, and p-cymene. Forty female Wister Albino rats were classified into five equal groups, the 1st served as normal group, the 2nd served as positive control group was given lead acetate (60 mg/kg) intra-peritoneal (IP), the third to fifth groups were treated with calcium disodium (EDTA) as chelating agent and summer savory essential oil in doses of (50 and 100mg/kg) respectively. All treatments were given IP concomitant with lead acetate for ten successive days. At the end of the experiment duration electrocardiogram (ECG), an open field test for the evaluation of psychological state, rotarod test as for the evaluation of locomotor coordination ability as well as anti-inflammatory and oxidative stress biomarkers in serum and histopathology of vital organs were performed. The investigations in this study show that the protective effect of high dose of summer savory essential oil is more than the low dose and that the essential oil of summer savory is a promising agent that can contribute to the protection of vital organs against the hazardous damaging effects of lead acetate.

Keywords: brain, heart, kidneys, lead acetate, liver, protective, summer savory

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375 Hypotensive effect of Cardiospermum halicacabum Linn. in Anesthetized Rats

Authors: Huma Shareef, Ghazala H. Rizwani, Ahsana Dar

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In traditional medicine Cardiospermum halicacabum L. (Sapindeaceae) is used against various ailments. In current investigation searching a new remedy that will available easily, non expensive, able to lower hypertension and standardize blood pressure, made us to develop an herbal medicine. Crude ethanol extract of C. halicacabum and its various fractions ethyl acetate and butanol showed a dose-dependent hypotensive effect in anaesthetized rats. The trachea was exposed and freed from connective tissue and incubated by cannula to facilitate spontaneous respiration. The right carotid artery and left jugular vein were cannulated with polyethylene tubing PE-50 for monitoring blood pressure changes via pressure transducer (Gould P23 ID) connected to a Grass model 79D polygraph and for i.v. injection, respectively. Drugs or the plant extracts were administered at a constant volume of 0.5 ml/kg, followed by injection of 0.2 ml of saline that flushed the cannula. Systolic, diastolic and mean arterial blood pressure (MABP) was measured in mm Hg and heart rate in beats/min. Ethanol extract of C. halicacabum showed a significant activity at 50 mg/kg dose. Ethyl acetate fraction (10, 20, 30, 40, and 50 mg/kg) induced dose dependent fall in systolic and diastolic blood pressure, heart rate of rats. At 10-30 mg/kg the hypotensive effect was non significantly reduced by 10 -15%. However, the extract at 40 mg/kg induced significant hypotensive effect calculated as 30.95±3.2% MABP and this effect persists till 50 mg/kg. The higher polar fraction (butanol) of the whole plant failed to produce any significant response against MABP at all the tested doses (10-50 mg/kg). C. halicacabum lowers blood pressure, exerts a dose-dependent hypotensive effect, can be used as hypotensor.

Keywords: cardiospermum halicacabum, calcium channel blocker, hypotensive, various extracts

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374 The Study of Platelet-Rich Plasma(PRP) on Wounds of OLEFT Rats Using Expression of MMP-2, MMP-9 mRNA

Authors: Ho Seong Shin

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Introduction: A research in relation to wound healing also showed that platelet-rich plasma (PRP) was effective on normal tissue regeneration. Nonetheless, there is no evidence that when platelet-rich plasma was applied on diabetic wound, it normalize diabetic wound healing process. In this study, we have analyzed matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) expression to know the effect of PRP on diabetic wounds using Reverse transcription-polymerase chain reaction (RT-PCR) of MMP-2, MMP-9 mRNA. Materials and Methods: Platelet-rich plasma (PRP) was prepared from blood of 6 rats. The whole 120-mL was added immediately to an anticoagulant. Citrate phosphonate dextrose(CPD) buffer (0.15 mg CPDmL) in a ratio of 1 mL of CPD buffer to 5 mL of blood. The blood was then centrifuged at 220g for 20minutes. The supernatant was saved to produce fibrin glue. The participate containing PRP was used for second centrifugation at 480g for 20 minutes. The pellet from the second centrifugation was saved and diluted with supernatant until the platelet concentration became 900,000/μL. Twenty male, 4week-old OLETF rats were underwent operation; each rat had two wounds created on left and right sides. The each wound of left side was treated with PRP gel, the wound of right side was treated with physiologic saline gauze. Results: RT-PCR analysis; The levels of MMP-2 mRNA in PRP applied tissues were positively related to postwounding days, whereas MMP-2 mRNA expression in saline-applied tissues remained in 5day after treatment. MMP-9 mRNA was undetectable in saline-applied tissues for either tissue, except 3day after treatment. Following PRP-applied tissues, MMP-9 mRNA expression was detected, with maximal expression being seen at third day. The levels of MMP-9 mRNA in PRP applied tissues were reported high intensity of optical density related to saline applied tissues.

Keywords: diabetes, MMP-2, MMP-9, OLETF, PRP, wound healing MMP-9

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