Search results for: experimental rats
Commenced in January 2007
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Paper Count: 7651

Search results for: experimental rats

7381 Protective Effect of Saponin Extract from the Root of Garcinia kola (Bitter Kola) against Paracetamol-Induced Hepatotoxicity in Albino Rats

Authors: Alli Smith Yemisi Rufina, Adanlawo Isaac Gbadura

Abstract:

Liver disorders are one of the major problems of the world. Despite its frequent occurrence, high morbidity, and high mortality, its medical management is currently inadequate. This study was designed to evaluate the Hepatoprotective effect of saponin extract of the root of Garcinia kola on the integrity of the liver of paracetamol induced Wistar albino rats. Twenty-five male adult Wistar albino rats were divided into five (5) groups. Group I, was the Control group that received distilled water only, group II was the negative control that received 2 g/kg of paracetamol on the 13th day, and group III, IV, and V were pre-treated with 100, 200 and 400 mg/kg of the saponin extract before inducing the liver damage on the 13th day with 2 g/kg of paracetamol. Twenty-four hours after administration, the rats were sacrificed, and blood samples were collected. The serum Alanine Transaminase (ALT), Aspartate Transaminase (AST), Alkaline Phosphatase (ALP) activities, Bilirubin and Conjugated Bilirubin, Glucose and Protein concentrations were evaluated. The liver was fixed immediately in Formalin and was processed and stained with Haematoxylin and Eosin (H&E). Administration of saponin extract from the root of Garcinia kola significantly decreased paracetamol induced elevated enzymes in the test group. Also, histological observations showed that saponin extract of the root of Garcinia kola exhibited a significant liver protection against the toxicant as evident by the cells trying to return to normal. Saponin extract from the root of Garcinia kola indicated a protection of the structural integrity of the hepatocytic cell membrane and regeneration of the damaged liver.

Keywords: hepatoprotective, liver damage, Garcinia kola, saponin, paracetamol

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7380 Potential Therapeutic Effect of Obestatin in Oral Mucositis

Authors: Agnieszka Stempniewicz, Piotr Ceranowicz, Wojciech Macyk, Jakub Cieszkowski, Beata Kuśnierz-Cabała, Katarzyna Gałązka, Zygmunt Warzecha

Abstract:

Objectives: There are numerous strategies for the prevention or treatment of oral mucositis. However, their effectiveness is limited and does not correspond to expectations. Recent studies have shown that obestatin exhibits a protective effect and accelerates the healing of gastrointestinal mucosa. The aim of the present study was to examine the influence of obestatin administration on oral ulcers in rats. Methods: lingual ulcers were induced by the use of acetic acid. Rats were treated twice a day intraperitoneally with saline or obestatin(4, 8, or 16 nmol/kg/dose) for five days. The study determined: lingual mucosa morphology, cell proliferation, mucosal blood flow, and mucosal pro-inflammatory interleukin-1β level(IL-1β). Results: In animals without induction of oral ulcers, treatment with obestatin was without any effect. Obestatin administration in rats with lingual ulcers increased the healing rate of these ulcers. Obestatin given at the dose of 8 or 16 nmol/kg/dose caused the strongest and similar therapeutic effect. This result was associated with a significant increase in blood flow and cell proliferation in gingival mucosa, as well as a significant decrease in IL-1β level. Conclusions: Obestatin accelerates the healing of lingual ulcers in rats. This therapeutic effect is well-correlated with an increase in blood flow and cell proliferation in oral mucosa, as well as a decrease in pro-inflammatory IL-1β levels. Obestatin is a potentially useful candidate for the prevention and treatment of oral mucositis. Acknowledgment: Agnieszka Stempniewicz acknowledges the support of InterDokMed project no. POWR.03.02.00- 00-I013/16.

Keywords: oral mucositis, ulcers, obestatin, lingual mucosa

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7379 Optimization and Evaluation of 177lu-Dotatoc as a Potential Agent for Peptide Receptor Radionuclide Therapy

Authors: H. Yousefnia, MS. Mousavi-Daramoroudi, S. Zolghadri, F. Abbasi-Davani

Abstract:

High expression of somatostatin receptors on a wide range of human tumours makes them as potential targets for peptide receptor radionuclide tomography. A series of octreotide analogues were synthesized while [DOTA-DPhe1, Tyr3]octreotide (DOTATOC) indicated advantageous properties in tumour models. In this study, 177Lu-DOTATOC was prepared with the radiochemical purity of higher than 99% in 30 min at the optimized condition. Biological behavior of the complex was studied after intravenous injection into the Syrian rats. Major difference uptake was observed compared to 177LuCl3 solution especially in somatostatin receptor-positive tissues such as pancreas and adrenal.

Keywords: Biodistribution, 177Lu, Octreotide, Syrian rats

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7378 AAV-Mediated Human Α-Synuclein Expression in a Rat Model of Parkinson's Disease –Further Characterization of PD Phenotype, Fine Motor Functional Effects as Well as Neurochemical and Neuropathological Changes over Time

Authors: R. Pussinen, V. Jankovic, U. Herzberg, M. Cerrada-Gimenez, T. Huhtala, A. Nurmi, T. Ahtoniemi

Abstract:

Targeted over-expression of human α-synuclein using viral-vector mediated gene delivery into the substantia nigra of rats and non-human primates has been reported to lead to dopaminergic cell loss and the formation of α-synuclein aggregates reminiscent of Lewy bodies. We have previously shown how AAV-mediated expression of α-synuclein is seen in the chronic phenotype of the rats over 16 week follow-up period. In the context of these findings, we attempted to further characterize this long term PD related functional and motor deficits as well as neurochemical and neuropathological changes in AAV-mediated α-synuclein transfection model in rats during chronic follow-up period. Different titers of recombinant AAV expressing human α-synuclein (A53T) were stereotaxically injected unilaterally into substantia nigra of Wistar rats. Rats were allowed to recover for 3 weeks prior to initial baseline behavioral testing with rotational asymmetry test, stepping test and cylinder test. A similar behavioral test battery was applied again at weeks 5, 9,12 and 15. In addition to traditionally used rat PD model tests, MotoRater test system, a high speed kinematic gait performance monitoring was applied during the follow-up period. Evaluation focused on animal gait between groups. Tremor analysis was performed on weeks 9, 12 and 15. In addition to behavioral end-points, neurochemical evaluation of dopamine and its metabolites were evaluated in striatum. Furthermore, integrity of the dopamine active transport (DAT) system was evaluated by using 123I- β-CIT and SPECT/CT imaging on weeks 3, 8 and 12 after AAV- α-synuclein transfection. Histopathology was examined from end-point samples at 3 or 12 weeks after AAV- α-synuclein transfection to evaluate dopaminergic cell viability and microglial (Iba-1) activation status in substantia nigra by using stereological analysis techniques. This study focused on the characterization and validation of previously published AAV- α-synuclein transfection model in rats but with the addition of novel end-points. We present the long term phenotype of AAV- α-synuclein transfected rats with traditionally used behavioral tests but also by using novel fine motor analysis techniques and tremor analysis which provide new insight to unilateral effects of AAV α-synuclein transfection. We also present data about neurochemical and neuropathological end-points for the dopaminergic system in the model and how well they correlate with behavioral phenotype.

Keywords: adeno-associated virus, alphasynuclein, animal model, Parkinson’s disease

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7377 Enhanced Wound Healing Efficacy of Cordycepin-Melittin Nanoconjugate in Excised Wounds of Diabetic Rats

Authors: Mohammed Flaih Alotaibi, Rasheed Ahemad Shaik, Mohammed Z. Nasrullah

Abstract:

Diabetic foot ulcers are the foremost global healthcare burden. Hyperglycemia in diabetics is incriminating in impeding wound healing and it can allow for more severe medical issues. The study was intended to establish a nanoconjugate of cordycepin-melittin (COR-MEL) and evaluate its healing effects in wounded diabetic rats. Diabetes induced by injecting streptozotocin intraperitoneally (50 mg/kg, body weight). Therefore, animals were classified into various groups; diabetic untreated, vehicle-treated, COR alone, MEL alone, and COR-MEL nanoconjugate treated, respectively. Animals with diabetes were exposed to excision and treated with Vehicle, COR, MEL, or COR-MEL nanoconjugate topically. After 14 days, the wounded skin was sliced and subjected to histological and biochemical assessments. The formulated nanoconjugate has a particle size of 253.5± 17.4 nm by a polydispersity index of 0.36 ± 0.05, and a zeta potential of 1.72 ± 0.3 mV. The study demonstrated an accelerated wound contraction in COR-MEL-treated diabetic rats, which was further validated by histological analysis. The nanoconjugate further exhibited antioxidant activities by inhibiting the accumulation of malondialdehyde and exhaustion of superoxide dismutase and glutathione peroxidase enzymatic activities. The nanoconjugate further demonstrated an enhanced anti-inflammatory activity by retarding the expression of proinflammatory cytokines (IL-6 and TNF-α). Additionally, the nanoconjugate exhibits a strong expression of growth factors (TGF-β1, VEGF-A, and PDGFR-β), indicating enrichment of proliferation. Likewise, nanoconjugate increased the concentration of hydroxyproline as well as the mRNA expression of collagen, type I, alpha 1. Thus, it is concluded that the nanoconjugate possesses a potent wound-healing activity in diabetic rats via antioxidant, anti-inflammatory, and pro-angiogenetic mechanisms.

Keywords: diabetic wounds, cordycepin, melittin, nanoconjugate, wound healing

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7376 Phytochemical Screening and Assessment of Hepatoprotective Activity of Geigeria alata Leaves Ethanolic Extract on Wistar Rats

Authors: Girgis Younan, Ikram Eltayeb

Abstract:

Geigeria alata belongs to the family Asteraceae, is an effective plant traditionally used in Sudan as a therapy for hepatic disease and as an antiepileptic, antispasmodic and to treat cough and intestinal complaints.The liver is responsible for many critical functions within the body and any liver disease or injury will result in the loss of those functions leading to significant damage in the body. Liver diseases cause increase in liver enzymes (AST, ALP ALT) and total bilirubin and a decrease in total blood protein level. The objective of this study is to investigate the hepato-protective activity of Geigeria alata leaves ethanolic extract. The plant leaves were extracted using 96% ethanol using Soxhlet apparatus. The hepatoprotective effect was determined using 25 wistar rats, the rats was divided to 5 groups, each group contain 5 rats: [Normal control group] receiving purified water, liver damage was induced in wistar rats by administering a 1:1 (v/v) mixture of CCl4 (1.25 ml/kg) and olive oil once at day four of the experiment [negative control group]. Two doses of extract [400mg/kg and 200mg/kg] was applied daily for 7 days, and standard drug Silymarin (200 mg/kg) were administered daily for 7 days to CCl4-treated rats. The degree of hepato-protective activity was evaluated by determining the hepatic marker enzymes AST, ALP, ALT, total Bilirubin and total proteins (TP). Results have shown that, the extract of G.alata leaves reduced the level of liver enzymes ALT, AST, ALP, total bilirubin and increased the level of total proteins. Since the levels of liver enzymes; bilirubin and total protein are considered as markers of liver function, the extract has proven to reduce the detrimental effects of liver toxicity induced using CCl4. The hepato-protective effect of extract on liver was found to be dose dependent, where the 400mg/kg dose of the extract exhibited higher activity than 200mg/kg dose. In addition, the effect of the higher dose (400mg/kg) of the extract was found to be higher than Silymarin standard drug. The result concludes that, G.alata leaves extract was found to exhibit profound hepato-protective activity, which justifies the traditional use of the plant for the treatment of hepatic diseases.

Keywords: alata, extract, geigeria, hepatoprotective

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7375 Grape Seed Extract in Prevention and Treatment of Liver Toxic Cirrhosis in Rats

Authors: S. Buloyan, V. Mamikonyan, H. Hakobyan, H. Harutyunyan, H. Gasparyan

Abstract:

The liver is the strongest regenerating organ of the organism, and even with 2/3 surgically removed, it can regenerate completely. Hence, liver cirrhosis may only develop when the regenerating system is off. We present the results of a comparative study of structural and functional characteristics of rat liver tissue under the conditions of toxic liver cirrhosis development, induced by carbon tetrachloride, and its prevention/treatment by natural compounds with antioxidant and immune stimulating action. Studies were made on Wister rats, weighing 120~140 g. Grape seeds extracts, separately and in combination with well known anticirrhotic drug ursodeoxycholic acid (ursodiol) have demonstrated effectiveness in prevention of liver cirrhosis development and its treatment.

Keywords: carbon tetrachloride, GSE, liver cirrhosis, prevention, treatment

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7374 Sub-Chronic Exposure to Dexamethasone Impairs Cognitive Function and Insulin in Prefrontal Cortex of Male Wistar Rats

Authors: A. Alli-Oluwafuyi, A. Amin, S. M. Fii, S. O. Amusa, A. Imam, N. T. Asogwa, W. I. Abdulmajeed, F. Olaseinde, B. V. Owoyele

Abstract:

Chronic stress or prolonged glucocorticoid administration impairs higher cognitive functions in rodents and humans. However, the mechanisms are not fully clear. Insulin and receptors are expressed in the brain and are involved in cognition. Insulin resistance accompanies Alzheimer’s disease and associated cognitive decline. The goal of this study was to evaluate the effects of sub-chronic administration of a glucocorticoid, dexamethasone (DEX) on behavior and biochemical changes in prefrontal cortex (PFC). Male Wistar rats were administered DEX (2, 4 & 8 mg/kg, IP) or saline for seven consecutive days and behavior was assessed in the following paradigms: “Y” maze, elevated plus maze, Morris’ water maze and novel object recognition (NOR) tests. Insulin, lactate dehydrogenase (LDH) and Superoxide Dismutase (SOD) activity were evaluated in homogenates of the prefrontal cortex. DEX-treated rats exhibited impaired prefrontal cortex function manifesting as reduced locomotion, impaired novel object exploration and impaired short- and long-term spatial memory compared to normal controls (p < 0.05). These effects were not consistently dose-dependent. These behavioral alterations were accompanied by a decrease in insulin concentration observed in PFC of 4 mg/kg DEX-treated rats compared to control (10μIU/mg vs. 50μIU/mg; p < 0.05) but not 2mg/kg. Furthermore, we report a modification of brain stress markers LDH and SOD (p > 0.05). These results indicate that prolonged activation of GCs disrupt prefrontal cortex function which may be related to insulin impairment. These effects may not be attributable to a non-specific elevation of oxidative stress in the brain. Future studies would evaluate mechanisms of GR-induced insulin loss.

Keywords: dexamethasone, insulin, memory, prefrontal cortex

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7373 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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7372 Study of the Biological Activity of a Ganglioside-Containing Drug (Cronassil) in an Experimental Model of Multiple Sclerosis

Authors: Hasmik V. Zanginyan, Gayane S. Ghazaryan, Laura M. Hovsepyan

Abstract:

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system that is induced in laboratory animals by developing an immune response against myelin epitopes. The typical clinical course is ascending palsy, which correlates with inflammation and tissue damage in the thoracolumbar spinal cord, although the optic nerves and brain (especially the subpial white matter and brainstem) are also often affected. With multiple sclerosis, there is a violation of lipid metabolism in myelin. When membrane lipids (glycosphingolipids, phospholipids) are disturbed, metabolites not only play a structural role in membranes but are also sources of secondary mediators that transmit multiple cellular signals. The purpose of this study was to investigate the effect of ganglioside as a therapeutic agent in experimental multiple sclerosis. The biological activity of a ganglioside-containing medicinal preparation (Cronassial) was evaluated in an experimental model of multiple sclerosis in laboratory animals. An experimental model of multiple sclerosis in rats was obtained by immunization with myelin basic protein (MBP), as well as homogenization of the spinal cord or brain. EAE was induced by administering a mixture of an encephalitogenic mixture (EGM) with Complete Freund’s Adjuvant. Mitochondrial fraction was isolated in a medium containing 0,25 M saccharose and 0, 01 M tris buffer, pH - 7,4, by a method of differential centrifugation on a K-24 centrifuge. Glutathione peroxidase activity was assessed by reduction reactions of hydrogen peroxide (H₂O₂) and lipid hydroperoxides (ROOH) in the presence of GSH. LPO activity was assessed by the amount of malondialdehyde (MDA) in the total homogenate and mitochondrial fraction of the spinal cord and brain of control and experimental autoimmune encephalomyelitis rats. MDA was assessed by a reaction with Thiobarbituric acid. For statistical data analysis on PNP, SPSS (Statistical Package for Social Science) package was used. The nature of the distribution of the obtained data was determined by the Kolmogorov-Smirnov criterion. The comparative analysis was performed using a nonparametric Mann-Whitney test. The differences were statistically significant when р ≤ 0,05 or р ≤ 0,01. Correlational analysis was conducted using a nonparametric Spearman test. In the work, refrigeratory centrifuge, spectrophotometer LKB Biochrom ULTROSPECII (Sweden), pH-meter PL-600 mrc (Israel), guanosine, and ATP (Sigma). The study of the process of lipid peroxidation in the total homogenate of the brain and spinal cord in experimental animals revealed an increase in the content of malonic dialdehyde. When applied, Cronassial observed normalization of lipid peroxidation processes. Reactive oxygen species, causing lipid peroxidation processes, can be toxic both for neurons and for oligodendrocytes that form myelin, causing a violation of their lipid composition. The high content of lipids in the brain and the uniqueness of their structure determines the nature of the development of LPO processes. The lipid layer of cellular and intracellular membranes performs two main functions -barrier and matrix (structural). Damage to the barrier leads to dysregulation of intracellular processes and severe disorders of cellular functions.

Keywords: experimental autoimmune encephalomyelitis, multiple sclerosis, neuroinflammation, therapy

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7371 Toxicological Study of Umbilicus rupesris L. Leaves: Hematological, Biochemical, and Histopathological Studies

Authors: Afaf Benhouda, Mouloud Yahia, Hachani Khadraoui, Asma Meddour, Souhila Benbia, Abdelmoudjib Ghecham, Djahida Benhouda

Abstract:

Umbilicus rupestris (UR) is an herbal medicine traditionally applied against the ignitions of the skin. The present paper aimed to study the acute and subacute toxicity with orally administered methanolic leaves extract of Umbilicus rupestris L (URMeOH). In acute toxicity tests, four groups of rats (n = 6/group/female) were orally treated with doses of 500, 1000, 1500 and 2000 mg/kg, and general behaviour, adverse effects, and mortality were recorded for up to 14 days. In subacute toxicity study, rats received URAMeOH by gavage at the doses of 100, 200 mg/kg/day (n = 6/group) for 28 days, and biochemical, hematological, and histopathological changes in tissues (liver, kidney) were determined. URMeOH did not produce any hazardous symptoms or death and in the acute toxicity test. Subacute treatment with URMeOH did not show any change in body weight, and hematological and biochemical profiles. In addition, no change was observed either in macroscopic or microscopic aspects of vital organs in rats. Our result showed that Umbilicus rupestris extract could be safe for human use.

Keywords: acute toxicity, biochemical parameters, hematological parameters, Umbilicus rupestris, subacute toxicity

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7370 Protective Effects of Ethanolic Purslane Extracts on Doxorubicin-Induced Hepatotoxicity in Albino Rats

Authors: Osama M. Ahmed, Walaa G. Hozayen, Haidy Tamer Abo Sree

Abstract:

The effect of doxorubicin (4 mg/kg b.w.week) without or with oral administration of ethanolic purslane (Portulaca oleracea) shoot (leaves and stems) extract (50 mg/kg b.w.day) or ethanolic purslane seeds extract (50 mg/kg b.w.day) co-treatments for 6 weeks was evaluated in adult male rats. There was an increase in serum levels of ALT, AST, ALP, GGT and total bilirubin. In addition, hepatic glutathine, glutathione transferase, peroxidase, SOD, CAT activities were decreased while lipid peroxidation in the liver was increased. Co-administration of ethanolic purslane and seed extracts successfully improved the adverse changes in the liver functions with an increase in antioxidants activities and reduction of lipid peroxidation.

Keywords: antioxidants, doxorubicin, hepatotoxicity, purslane

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7369 Chemical Profiling of Hymenocardia acida Stem Bark Extract and Modulation of Selected Antioxidant and Esterase Enzymes in Kidney and Heart Ofwistar Rats

Authors: Adeleke G. E., Bello M. A., Abdulateef R. B., Olasinde T. T., Oriaje K. O., AransiI A., Elaigwu K. O., Omidoyin O. S., Shoyinka E. D., Awoyomi M. B., Akano M., Adaramoye O. A.

Abstract:

Hymenocardia acidatul belongs to the genus, Hymenocardiaceae, which is widely distributed in Africa. Both the leaf and stem bark of the plant have been used in the treatment of several diseases. The present study examined the chemical constituents of the H. acida stem bark extract (HASBE) and its effects on some antioxidant indices and esterase enzymes in female Wistar rats. The HASBE was obtained by Soxhlet extraction using methanol and then subjected to Atomic Absorption Spectroscopy (AAS) for elemental analysis, and Fourier-Transform Infrared (FT-IR) spectroscopy, ultraviolet (UV) spectroscopy, for functional group analysis, while High-performance liquid chromatography (HPLC), and Gas Chromatography-Flame ionization detection (GC-FID) were carried out for compound identification. Forty-eight female Wistar rats were assigned into eight groups of six rats each and separately administered orally with normal saline (Control), 50, 100, 150, 200, 250, 300, 350 mg/kg of HASBE twice per week for eight weeks. The rats were sacrificed under chloroform anesthesia, and kidneys and heart were excised and processed to obtain homogenates. The levels of superoxide dismutase (SOD), catalase, Malondialdehyde (MDA), glutathione peroxidase (GPx), acetylcholinesterase (AChE), and carboxylesterase (CE) were determined spectrophotometrically. The AAS of HASBE shows the presence of eight elements, including Cobalt (0.303), Copper (0.222), Zinc (0.137), Iron (2.027), Nickel (1.304), Chromium (0.313), Manganese (0.213), and Magnesium (0.337 ppm). The FT-IR result of HASBE shows four peaks at 2961.4, 2926.0, 1056.7, and 1034.3 cm-1, while UV analysis shows a maximum absorbance (0.522) at 205 nm. The HPLC spectrum of HASBE indicates the presence of four major compounds, including orientin (77%), β-sitosterol (6.58%), rutin (5.02%), and betulinic acid (3.33%), while GC-FID result shows five major compounds, including rutin (53.27%), orientin (13.06%) and stigmasterol (11.73%), hymenocardine (6.43%) and homopterocarpin (5.29%). The SOD activity was significantly (p < 0.05) lowered in the kidney but elevated in the heart, while catalase was elevated in both organs relative to control rats. The GPx activity was significantly elevated only in the kidney, while MDA was not significantly (p > 0.05) affected in the two organs compared with controls. The activity of AChE was significantly elevated in both organs, while CE activity was elevated only in the kidney relative to control rats. The present study reveals that Hymenocardia acida stem bark extract majorly contains orientin, rutin, stigmasterol, hymenocardine, β-sitosterol, homopterocarpin, and betulinic acid. In addition, these compounds could possibly enhance redox status and esterase activities in the kidney and heart of Wistar rats.

Keywords: hymenocardia acida, elemental analysis, compounds identification, redox status, organs

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7368 Proprotein Convertase Subtilisin/Kexin Type 9 Enhances Arterial Medial Calcification in a Uremic Rat Model of Chronic Kidney Disease

Authors: Maria Giovanna Lupo, Marina Camera, Marcello Rattazzi, Nicola Ferri

Abstract:

A complex interplay among chronic kidney disease, lipid metabolism and aortic calcification has been recognized starting from results of many clinical and experimental studies. Here we investigated the influence of kidney function on PCSK9 levels, both in uremic rats and in clinical observation study, and its potential direct action on cultured smooth muscle cells (SMCs) calcification. In a cohort of 594 subjects enrolled in a single centre, observational, cross-sectional and longitudinal study, a negative association between GFR and plasma PCSK9 was found. Atherosclerotic cardiovascular disease (ASCVD), as co-morbidity, further increased PCSK9 plasma levels. Diet-induced uremic condition in rats, induced aortic calcification and increased total cholesterol and PCSK9 levels in plasma, livers and kidneys. Immunohistochemical analysis confirmed PCSK9 expression in aortic SMCs. SMCs overexpressing PCSK9 (SMCsPCSK9), cultured for 7-days in a pro-calcification environment (2.0mM or 2.4mM inorganic phosphate, Pi) showed a significantly higher extracellular calcium (Ca2+) deposition compared to mocked SMCs. Under the same experimental conditions, the addition of exogenous recombinant PCSK9 did not increase the extracellular calcification of SMCs. By flow cytometry analysis we showed that SMCsPCSK9, in response to 2.4mM Pi, released higher number of extracellular vesicles (EVs) positive for three tetraspanin molecules, such as CD63, CD9, and CD81. EVs derived from SMCsPCSK9 tended to be more enriched in calcium and alkaline phosphatase (ALPL), compared to EVs from mocks SMCs. In conclusion, our study reveals a direct role of PCSK9 on vascular calcification induced by higher inorganic phosphate levels associated to CKD condition. This effect appears to be mediated by a positive effect of endogenous PCSK9 on the release of EVs containing Ca2+ and ALP, which facilitate the deposition inorganic calcium phosphate crystals.

Keywords: PCSK9, calcification, extracellular vesicles, chronic kidney disease

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7367 Insufficiency of Cardioprotection at Adaptation to Chronic Hypoxia and at Remote Postconditioning in Young and Aged Rats with Metabolic Syndrome, the Role of Metabolic Disorders or Opioid Signaling

Authors: Natalia V. Naryzhnaya, Alexandr V. Mukhomedzyanov, Ivan A. Derkachev, Boris K. Kurbatov, Leonid N. Maslov

Abstract:

Background: Techniques of adaptation to hypoxia and remote postconditioning (RPost) have great prospects for use in the clinic. However, recent studies have shown low efficacy of remote postconditioning in patients with AMI. We hypothesize that the reasons for this inefficiency may be metabolic disorders, which are very common, especially in patients with cardiovascular disease, and age of patients. The purpose of the study was to reveal the effectiveness of adaptation to chronic hypoxia and RPost. To determine the possible relationship between the decrease in the effectiveness of projective impacts and disorders of carbohydrate and lipid metabolism. Design: The study was carried out on Wistar rats 60 day old. MetS was induced by high-carbohydrate, high-fat diet (HСHFD). Modeling MS led to the formation of obesity, hypertension, impaired lipid and carbohydrate metabolism, hyperleptinemia, and moderate stress. Groups with adaptation to chronic hypoxia were subjected to hypoxia for 21 days at 12% O2 and 0.3% CO2 after complete of HСHFD. All animals were subjected to 45 min coronary occlusion and 120 min reperfusion. Groups with RPost, immediately after the end of ischemia, tourniquets were applied to the hind limbs in the area of the hip joint (3 times in the mode of 5 min ischemia, 5 min reperfusion). Results: RPost led to a twofold reduction of infarct size in rats with intact metabolism (р < 0.0001), while in rats with MetS, a decrease in infarct size during RPost was 25 % (p = 0.00003). A direct correlation was found between of infarct size during RPost and the serum leptin level of rats with MetC (r = 0.85). The presented data suggested that a decrease in the efficiency of remote postconditioning in rats with diet-induced metabolic syndrome depends on serum leptin. Chronic hypoxia resulted in a 38% reduced in infarct size in metabolically intact rats. The decrease of cardioprotection was observed in rats with chronic hypoxia and MetS. Infarct size showed a direct correlation with impaired glucose tolerance (AUC, glucose tolerance test, r = 0.034) and serum triglyceride levels (r = 0.39). Our study showed the dependence of cardioprotection in rats with metabolic syndrome during chronic hypoxia and DPost on opioids in the blood serum and myocardium, protein kinase C and NO synthase activity. Conclusion: The results obtained showed that the infarct-limiting efficiency of adaptation to hypoxia and remote postconditioning is reduced or completely absent in animals with metabolic syndrome. The increase in the infarction, in this case, directly depends on the disturbances in carbohydrate. lipid metabolism and opioids signaling. Funding: Investigation of effectiveness of chronic hypoxia at the metabolic syndrome was carried out within the support of Russian Science Foundation Grant 22-15-00048. Studies of the mechanisms of arterial hypertension in induced metabolic syndrome were carried out within the framework of the state assignment (122020300042-4). The work was performed using the Center for Collective Use "Medical Genomics".

Keywords: chronic hypoxia, opioids, remote postconditioning, metabolic syndrome

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7366 Carvedilol Ameliorates Potassium Dichromate-Induced Acute Renal Injury in Rats: Plausible Role of Inflammation and Apoptosis

Authors: Bidya Dhar Sahu, Meghana Koneru, R. Shyam Sunder, Ramakrishna Sistla

Abstract:

Environmental and occupational exposure to hexavalent chromium [Cr(VI)] via textile manufacture, metallurgy, spray paints, stainless steel industries, drinking water containing chromium are often known to cause acute renal injury in humans and animals. Nephrotoxicity is the major effect of chromium poisoning. In the present study, we investigated the potential renoprotective effect and underlying mechanisms of carvedilol using rat model of potassium dichromate (K2Cr2O7)-induced nephrotoxicity. Exploration of the underlying mechanisms of carvedilol revealed that carvedilol attenuated nuclear translocation and DNA binding activity of NF-κB (p65), restored antioxidant and mitochondrial respiratory enzyme activities and attenuated apoptosis related protein expressions in kidney tissues. The serum levels of TNF-α, the renal iNOS and myeloperoxidase activity were significantly decreased in carvedilol pre-treated K2Cr2O7-induced nephrotoxic rats. These results were further supported and confirmed by histological findings. In conclusion, the findings of the present study demonstrated that carvedilol is an effective chemoprotectant against K2Cr2O7-induced nephrotoxicity in rats.

Keywords: apoptosis, carvedilol, inflammation, potassium dichromate-induced nephrotoxicity, applied pharmacology

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7365 Effect of Electromagnetic Radiation on Reproductive System of Male Rat

Authors: Rohit Gautam, Kumari Vandana Singh, Jayprakash Nirala, Nina Nancy Murmu, Ramovatar Meena, Paulraj Rajamani

Abstract:

Mobile phones have become a vital part of everyone’s life. Mobile phone and mobile phone towers emit RF-EMR (Radiofrequency Electromagnetic Radiation), which becomes a cause of concern to the general public. The study was designed to evaluate the effect of 3G (RF-EMR) on the reproductive system of male Wistar rats. Adult male Wistar rats were used for the study. Animals were divided into two groups, RF-exposed, and sham-exposed (control). RF-exposed rats were exposed to radio frequency radiation (2100 MHz) for 2 hours/day for 45 days. Emitted power density and specific absorption rate (SAR) values were measured during exposure. At the end of the exposure, testis and epididymis were excised out, and their weights were recorded. Sperm cell count, morphology, viability, and reactive oxygen species (ROS) levels were checked. Lipid peroxidation and sperm mitochondrial activity were measured. Histopathology of testis and ultrastructure analysis of sperm were also checked. Result showed a decrease in organ weight and sperm count with alteration in the sperm morphology in exposed group rats. A significant decrease in sperm viability, membrane integrity, and mitochondrial activity was found. Also, an increase in lipid peroxidation and ROS level were found in exposed group animals as compared to control. It may be concluded that exposure to radiofrequency radiation emits from mobile phones leads to oxidative stress-mediated changes in reproductive parameters.

Keywords: electromagnetic radiation, oxidative stress, reactive oxygen species, sperm

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7364 The Protective Effects of Naringenin on Iodoacetamide-Induced Ulcerative Colitis in Rats

Authors: Yomna T. Abdou, Hala F. Zaki, Sanaa A. Kenawy

Abstract:

Naringenin is a flavanone, a type of flavonoid, found in fruits such as grapefruit, oranges, and tomatoes, was found to possess antioxidant, anti-inflammatory and antitumor effects. The present study was conducted to investigate the protective effect of naringenin on iodoacetamide-induced ulcerative colitis (UC) in rats. Male Wistar rats were pretreated with sulfasalazine (300 mg/kg, p.o.) as standard anti-inflammatory drug or naringenin (50 mg/kg, p.o.) for 7 consecutive days then UC was induced by intracolon administration of 0.1 ml (2%) iodoacetamide dissolved in 1% methylcelluose. One week later, animals were scarificed and the colonic tissues were dissected. Colon inflammation was evident by elevation in colon tumor necrosis factor alpha (TNFα) and interleukin-8 (IL-8) as well as inducible nitric oxide synthase (iNOS) enzyme, prostaglandin- E2 (PG-E2) and myeloperoxidase (MPO) activities. Additionally, oxidative stress was manifested by increased colon lipoperoxidation (MDA), glutathione (GSH) depletion, elevated nitric oxide (NO) content and glutathione peroxidase (GPx) activity. Pretreatment with naringenin largely mitigated these alterations. The present study reinforces the hypothetical use of naringenin as an anti-inflammatory complement to conventional UC treatment and could be considered in the dietary prevention of intestinal inflammation and related disorders.

Keywords: iodoacetamide, naringenin, sulfasalazine, ulcerative colitis

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7363 Effects of Paroxetine on Biochemical Parameters and Reproductive Function in Male Rats

Authors: Rachid Mosbah, Aziez Chettoum, Zouhir Djerrou, Alberto Mantovani

Abstract:

Selective serotonin reuptake inhibitors (SSRI) are a class of molecules used in treating depression, anxiety, and mood disorders. Paroxetine (PRT) is one of the mostly prescribed antidepressant which has attracted great attention regarding its side effects in recent years. This study was planned to assess the adverse effects of PRT on the biochemical parameters and reproductive system. Fourteen male Wistar rats were randomly allocated into two groups (7 rats or each): control and treated with PRT at dose of 5mg/kg.bw for two weeks. At the end of the experiment, blood was collected from retro orbital plexus for measuring the biochemical parameters, whereas the reproductive organs were removed for measuring semen quality and the histological investigations. Results showed that PRT induced significant changes in some biochemical parameters and alteration of semen quality including sperm count, spermatids number and sperm viability, motility, and abnormalities. The histopathological examinations of testis and epididymis revealed an alteration of spermatogenesis, cellular disorganization and vacuolization, enlargement of interstitial space, shrinkage and degenerative changes in the epithelium of seminiferous and epididymal tubules with few to nil numbers of spermatozoa in their lumen. In conclusion, PRT treatment caused changes in some biochemical parameters and sperm profile as well as histopathologic effects of reproductive organs.

Keywords: antidepressant, biochemical parameters, reproductive function, paroxetine

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7362 Effects of Intracerebroventricular Injection of Ghrelin and Aerobic Exercise on Passive Avoidance Memory and Anxiety in Adult Male Wistar Rats

Authors: Mohaya Farzin, Parvin Babaei, Mohammad Rostampour

Abstract:

Ghrelin plays a considerable role in important neurological effects related to food intake and energy homeostasis. As was found, regular physical activity may make available significant improvements to cognitive functions in various behavioral situations. Anxiety is one of the main concerns of the modern world, affecting millions of individuals’ health. There are contradictory results regarding ghrelin's effects on anxiety-like behavior, and the plasma level of this peptide is increased during physical activity. Here we aimed to evaluate the coincident effects of exogenous ghrelin and aerobic exercise on anxiety-like behavior and passive avoidance memory in Wistar rats. Forty-five male Wistar rats (250 ± 20 g) were divided into 9 groups (n=5) and received intra-hippocampal injections of 3.0 nmol ghrelin and performed aerobic exercise training for 8 weeks. Control groups received the same volume of saline and diazepam as negative and positive control groups, respectively. Learning and memory were estimated using a shuttle box apparatus, and anxiety-like behavior was recorded by an elevated plus-maze test (EPM). Data were analyzed by ANOVA test, and p<0.05 was considered significant. Our findings showed that the combined effect of ghrelin and aerobic exercise improves the acquisition, consolidation, and retrieval of passive avoidance memory in Wistar rats. Furthermore, it is supposed that the ghrelin receiving group spent less time in open arms and fewer open arms entries compared with the control group (p<0.05). However, exercising Wistar rats spent more time in the open arm zone in comparison with the control group (p<0.05). The exercise + Ghrelin administration established reduced anxiety (p<0.05). The results of this study demonstrate that aerobic exercise contributes to an increase in the endogenous production of ghrelin, and physical activity alleviates anxiety-related behaviors induced by intra-hippocampal injection of ghrelin. In general, exercise and ghrelin can reduce anxiety and improve memory.

Keywords: anxiety, ghrelin, aerobic exercise, learning, passive avoidance memory

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7361 Oral Toxicity of Low Doses of Fungicides, Propinebe, Propiconazole and Their Mixtures in the Male Rat

Authors: Mallem Leila, Aiche Mohamed Amine, Boulakoud Mohamed Salah

Abstract:

A number of chemical compounds are being used to protect agricultural crops from diseases. Residues of these chemicals lead to environmental pollution and pose some threat to non target organisms, human and animal. The aim of this study is to detect the toxicity of these fungicides and their mixtures in the fertility and biochemical’s parameters in the rat. The male of rats (28) were used, they were divided in four groups (7 rats of each group) and one group was used as control. Rats were dosed orally with propiconazole (60 mg/kg body weight/day), propinebe (100 mg/Kg body weight/day) and their mixture (50:50) for 4 weeks. Animals were observed for clinical toxicity. At the end of treatment period, animals of all groups were scarified and samples of different organs were fixed in the formol 10% for histopathological study, and blood was collected for hematological and biochemical’s analysis. The results indicated that the fungicide and their mixture of fungicides were toxic in the treated animals. The semen study showed a decrease in the count, mobility and speed of spermatozoa in all treated group especially those dosed with the mixture and Propiconazole, it was also a decrease in the weight of the testis and epidydimis in the treated group as compared with control. Remarquable histological changes were observed in the testis and epidydimis and liver in the group treated with mixture.

Keywords: fungicides, mixture, fertility, hematological, biochemical's parameters

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7360 Biochemical Studies on the Effects of Cymbopogon citratus (Lemon Grass) on Wistar Albino Rats

Authors: Adegbegi Ademuyiwa Joshua, Onoagbe Iyare

Abstract:

Medicinal plants have been recognized to have therapeutic effects and they may also have toxic side effects. The present study was undertaken to investigate the effect of extracts of Cymbopogon citratus on normal rats. Blood glucose levels of all animals were determined. Biochemical studies carried out to determine the oxidative status by measuring activities of superoxide dismutase (SOD) and catalase (CAT), and in the liver, kidney and pancrease. Oral administration of ethanolic and aqueous extract of C. citratus at a doses of 200 mg/kg body weight, for a period of 30 days, caused a significant (p<0.05) reduction in blood glucose levels. Effect on hormonal profile (TSH, T3, and T4) was also determined, and was found to be significantly higher in all the administered groups when compared with control. Lipid profiles levels; Total cholesterols, triglycerides, high density lipoprotein-cholesterol and low density lipoprotein-cholesterol were significantly (p>0.05) higher for all treated rats as compared against control. SOD, catalase, GSH and Vitamin C activities in the tissues (liver, kidney and pancrease) of the rats treated with the medicinal plants were generally higher or statistical slightly similar to control. Histopathology result showed that both ethanolic and aqueous extracts (200 mg/kg body weight) of C. citratus was safer as no adverse effects were observed in the organs examined. Findings in this study showed that this plant has hypoglycemic properties and did not exert oxidative damage; in some instances, particularly in the liver, kidney and pancreas as well as its relative safety and possible use for weight gain.

Keywords: medicinal plants, blood glucose, cymbopogon citratus, hypoglycaemic, oxidative status

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7359 Human Absorbed Dose Estimation of a New In-111 Imaging Agent Based on Rat Data

Authors: H. Yousefnia, S. Zolghadri

Abstract:

The measurement of organ radiation exposure dose is one of the most important steps to be taken initially, for developing a new radiopharmaceutical. In this study, the dosimetric studies of a novel agent for SPECT-imaging of the bone metastasis, 111In-1,4,7,10-tetraazacyclododecane-1,4,7,10 tetraethylene phosphonic acid (111In-DOTMP) complex, have been carried out to estimate the dose in human organs based on the data derived from rats. The radiolabeled complex was prepared with high radiochemical purity in the optimal conditions. Biodistribution studies of the complex was investigated in the male Syrian rats at selected times after injection (2, 4, 24 and 48 h). The human absorbed dose estimation of the complex was made based on data derived from the rats by the radiation absorbed dose assessment resource (RADAR) method. 111In-DOTMP complex was prepared with high radiochemical purity of >99% (ITLC). Total body effective absorbed dose for 111In-DOTMP was 0.061 mSv/MBq. This value is comparable to the other 111In clinically used complexes. The results show that the dose with respect to the critical organs is satisfactory within the acceptable range for diagnostic nuclear medicine procedures. Generally, 111In-DOTMP has interesting characteristics and can be considered as a viable agent for SPECT-imaging of the bone metastasis in the near future.

Keywords: In-111, DOTMP, Internal Dosimetry, RADAR

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7358 Impaired Transient Receptor Potential Vanilloid 4-Mediated Dilation of Mesenteric Arteries in Spontaneously Hypertensive Rats

Authors: Ammar Boudaka, Maryam Al-Suleimani, Hajar BaOmar, Intisar Al-Lawati, Fahad Zadjali

Abstract:

Background: Hypertension is increasingly becoming a matter of medical and public health importance. The maintenance of normal blood pressure requires a balance between cardiac output and total peripheral resistance. The endothelium, through the release of vasodilating factors, plays an important role in the control of total peripheral resistance and hence blood pressure homeostasis. Transient Receptor Potential Vanilloid type 4 (TRPV4) is a mechanosensitive non-selective cation channel that is expressed on the endothelium and contributes to endothelium-mediated vasodilation. So far, no data are available about the morphological and functional status of this channel in hypertensive cases. Objectives: This study aimed to investigate whether there is any difference in the morphological and functional features of TRPV4 in the mesenteric artery of normotensive and hypertensive rats. Methods: Functional feature of TRPV4 in four experimental animal groups: young and adult Wistar-Kyoto rats (WKY-Y and WKY-A), young and adult spontaneously hypertensive rats (SHR-Y and SHR-A), was studied by adding 5 µM 4αPDD (TRPV4 agonist) to mesenteric arteries mounted in a four-chamber wire myograph and pre-contracted with 4 µM phenylephrine. The 4αPDD-induced response was investigated in the presence and absence of 1 µM HC067047 (TRPV4 antagonist), 100 µM L-NAME (nitric oxide synthase inhibitor), and endothelium. The morphological distribution of TRPV4 in the wall of rat mesenteric arteries was investigated by immunostaining. Real-time PCR was used in order to investigate mRNA expression level of TRPV4 in the mesenteric arteries of the four groups. The collected data were expressed as mean ± S.E.M. with n equal to the number of animals used (one vessel was taken from each rat). To determine the level of significance, statistical comparisons were performed using the student’s t-test and considered to be significantly different at p<0.05. Results: 4αPDD induced a relaxation response in the mesenteric arterial preparations (WKY-Y: 85.98% ± 4.18; n = 5) that was markedly inhibited by HC067047 (18.30% ± 2.86; n= 5; p<0.05), endothelium removal (19.93% ± 1.50; n = 5; p<0.05) and L-NAME (28.18% ± 3.09; n = 5; p<0.05). The 4αPDD-induced relaxation was significantly lower in SHR-Y compared to WKY-Y (SHR-Y: 70.96% ± 3.65; n = 6, WKY-Y: 85.98% ± 4.18; n = 5-6, p<0.05. Moreover, the 4αPDD-induced response was significantly lower in WKY-A than WKY-Y (WKY-A: 75.58 ± 1.30; n = 5, WKY-Y: 85.98% ± 4.18; n = 5, p<0.05). Immunostaining study showed immunofluorescent signal confined to the endothelial layer of the mesenteric arteries. The expression of TRPV4 mRNA in SHR-Y was significantly lower than in WKY-Y (SHR-Y; 0.67RU ± 0.34; n = 4, WKY-Y: 2.34RU ± 0.15; n = 4, p<0.05). Furthermore, TRPV4 mRNA expression in WKY-A was lower than its expression in WKY-Y (WKY-A: 0.62RU ± 0.37; n = 4, WKY-Y: 2.34RU ± 0.15; n = 4, p<0.05). Conclusion: Stimulation of TRPV4, which is expressed on the endothelium of rat mesenteric artery, triggers an endothelium-mediated relaxation response that markedly decreases with hypertension and growing up changes due to downregulation of TRPV4 expression.

Keywords: hypertension, endothelium, mesenteric artery, TRPV4

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7357 Fatty Acid Translocase (Cd36), Energy Substrate Utilization, and Insulin Signaling in Brown Adipose Tissue in Spontaneously Hypertensive Rats

Authors: Michal Pravenec, Miroslava Simakova, Jan Silhavy

Abstract:

Brown adipose tissue (BAT) plays an important role in lipid and glucose metabolism in rodents and possibly also in humans. Recently, using systems genetics approach in the BAT from BXH/HXB recombinant inbred strains, derived from the SHR (spontaneously hypertensive rat) and BN (Brown Norway) progenitors, we identified Cd36 (fatty acid translocase) as the hub gene of co-expression module associated with BAT relative weight and function. An important aspect of BAT biology is to better understand the mechanisms regulating the uptake and utilization of fatty acids and glucose. Accordingly, BAT function in the SHR that harbors mutant nonfunctional Cd36 variant (hereafter referred to as SHR-Cd36⁻/⁻) was compared with SHR transgenic line expressing wild type Cd36 under control of a universal promoter (hereafter referred to as SHR-Cd36⁺/⁺). BAT was incubated in media containing insulin and 14C-U-glucose alone or 14C-U-glucose together with palmitate. Incorporation of glucose into BAT lipids was significantly higher in SHR-Cd36⁺/⁺ versus SHR-Cd36⁻/⁻ rats when incubation media contained glucose alone (SHR-Cd36⁻/⁻ 591 ± 75 vs. SHR-Cd36⁺/⁺ 1036 ± 135 nmol/gl./2h; P < 0.005). Adding palmitate into incubation media had no effect in SHR-Cd36⁻/⁻ rats but significantly reduced glucose incorporation into BAT lipids in SHR-Cd36⁺/⁺ (SHR-Cd36⁻/⁻ 543 ± 55 vs. SHR-Cd36⁺/⁺ 766 ± 75 nmol/gl./2h; P < 0.05 denotes significant Cd36 x palmitate interaction determined by two-way ANOVA). This Cd36-dependent reduced glucose uptake in SHR-Cd36⁺/⁺ BAT was likely secondary to increased palmitate incorporation and utilization due to the presence of wild type Cd36 fatty acid translocase in transgenic rats. This possibility is supported by increased incorporation of 14C-U-palmitate into BAT lipids in the presence of both palmitate and glucose in incubation media (palmitate alone: SHR-Cd36⁻/⁻ 870 ± 21 vs. SHR-Cd36⁺/⁺ 899 ± 42; glucose+palmitate: SHR-Cd36⁻/⁻ 899 ± 47 vs. SHR-Cd36⁺/⁺ 1460 ± 111 nmol/palm./2h; P < 0.05 denotes significant Cd36 x glucose interaction determined by two-way ANOVA). It is possible that addition of glucose into the incubation media increased palmitate incorporation into BAT lipids in SHR-Cd36⁺/⁺ rats because of glucose availability for glycerol phosphate production and increased triglyceride synthesis. These changes in glucose and palmitate incorporation into BAT lipids were associated with significant differential expression of Irs1, Irs2, Slc2a4 and Foxo1 genes involved in insulin signaling and glucose metabolism only in SHR-Cd36⁺/⁺ rats which suggests Cd36-dependent effects on insulin action. In conclusion, these results provide compelling evidence that Cd36 plays an important role in BAT insulin signaling and energy substrate utilization.

Keywords: brown adipose tissue, Cd36, energy substrate utilization, insulin signaling, spontaneously hypertensive rat

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7356 Hepatoprotective Effect of Oleuropein against Cisplatin-Induced Liver Damage in Rat

Authors: Salim Cerig, Fatime Geyikoglu, Murat Bakir, Suat Colak, Merve Sonmez, Kubra Koc

Abstract:

Cisplatin (CIS) is one of the most effective an anticancer drug and also toxic to cells by activating oxidative stress. Oleuropein (OLE) has key role against oxidative stress in mammalian cells, but the role of this antioxidant in the toxicity of CIS remains unknown. The aim of the present study was to investigate the efficacy of OLE on CIS-induced liver damages in male rats. With this aim, male Sprague Dawley rats were randomly assigned to one of eight groups: Control group; the group treated with 7 mg/kg/day CIS; the groups treated with 50, 100 and 200 mg/kg/day OLE (i.p.); and the groups treated with OLE for three days starting at 24 h following CIS injection. After 4 days of injections, serum was provided to assess the blood AST, ALT and LDH values. The liver tissues were removed for histological, biochemical (TAC, TOS and MDA) and genotoxic evaluations. In the CIS treated group, the whole liver tissue showed significant histological changes. Also, CIS significantly increased both the incidence of oxidative stress and the induction of 8-hydroxy-deoxyguanosine (8-OH-dG). Moreover, the rats taking CIS have abnormal results on liver function tests. However, these parameters reached to the normal range after administration of OLE for 3 days. Finally, OLE demonstrated an acceptable high potential and was effective in attenuating CIS-induced liver injury. In this trial, the 200 mg/kg dose of OLE firstly appeared to induce the most optimal protective response.

Keywords: antioxidant response, cisplatin, histology, liver, oleuropein, 8-OhdG

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7355 Green Tea Extract: Its Potential Protective Effect on Bleomycin Induced Lung Injuries in Rats

Authors: Azza EL-Medany, Jamila EL-Medany

Abstract:

Lung fibrosis is a common side effect of the chemotherapeutic agent, bleomycin. Current evidence suggests that reactive oxygen species may play a key role in the development of lung fibrosis. The present work studied the effect of green tea extract on bleomycin–induced lung fibrosis in rats. Animals were divided into three groups: (1) Saline control group; (2) bleomycin group in which rats were injected with bleomycin (15mg/kg,i.p.) three times a week for four weeks; (3) bleomycin and green tea group in which green tea extract was given to rats (100mg/kg/day, p.o) a week prior to bleomycin and daily during bleomycin injections for 4 weeks until the end of the experiment. Bleomycin–induced pulmonary injury and lung fibrosis that was indicated by increased lung hydroxyproline content, elevated nitric oxide synthase, myeoloperoxidase (MPO), platelet activating factor (PAF), tumor necrosis factor α (TNF_α), transforming growth factor 1β (TGF1β) and angiotensin converting enzyme (ACE) activity in lung tissues. On the other hand, bleomycin induced a reduction in reduced glutathione concentration (GSH). Moreover, bleomycin resulted in a severe histological changes in lung tissues revealed as lymphocytes and neutrophils infiltration, increased collagen deposition and fibrosis. Co-administration of bleomycin and green tea extract reduced bleomycin–induced lung injury as evaluated by the significant reduction in hydroxyproline content, nitric oxide synthase activity, levels of MPO, PAF, TNF-α, and ACE in lung tissues. Furthermore, green tea extract ameliorated bleomycin– induced reduction in GSH concentration. Finally, histological evidence supported the ability of green tea extract to attenuate bleomycin–induced lung fibrosis and consolidation. Thus, the finding of the present study provides that green tea may serve as a novel target for potential therapeutic treatment of lung fibrosis.

Keywords: bleomycin, lung fibrosis, green tea, oxygen species

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7354 Effect Indol Acetic Acid on Liver of Albino Rats

Authors: Ezaldin A. M. Mohammed, Youssef K. H. Abdalhafid, Masoud. M. Zatout

Abstract:

The study aims to clarify the toxic effect of plant hormones, which are widely used in agriculture. One of these is the plant hormones (indole acetic acid); has been ٳata hormone to rats at 100 ppm salt solution of 0.2 per day after day for a period of forty days before conception until the fourteenth day or sixteenth or childbirth. Treatment brought about a marked shortage in the rate of increase in the weight of mice., And a percentage of the weight of the liver there was a distinct increase in the relative weight of the liver. As well as the increase in pathological changes and increase the size of the nuclei and Kupffer cell, as noted widespread and dense clusters of inflammatory cells accompanied by about the erosion of liver tissue and blood ٳrchah. Biochemical analyzes showed a marked decrease of the liver in antioxidant enzymes and an increase in the rate of free radicals. It was also noted an increase in cases of abortion. The owner of so many birth defects. It was also noted the lack of body weight in fetuses and increase the absorption rate of embryos in fetuses of mothers treatment compared to the control group. Showed microscopic examinations of the liver of mice born in the transaction and the decay in the presence of hepatic cells and edema, blood vessels and increase the rate of cell death.

Keywords: indol acetic acid, liver, pathological changes, albino rats

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7353 Meld of Lactobacillus and Rangiferinus for Emendation of Endotoxemia in Alcoholic Liver Damage in Rats

Authors: Shukla Ila, Azmi Lubna, S. S. Gupta, Ch. V. Rao

Abstract:

Oxidative stress has been increasingly associated with the induction and progression of liver damage. The current study was conducted to record the effect of combination of Lactobacillus and Lichen rangiferinus extract (LRE + Lac) on the severity of injury in experimental alcoholic liver disease and how it affects plasma levels of prostaglandin E2, endotoxin, thromboxane B2, and leukotriene B4. Male Wistar rats were grouped into five comprising six animals in each group. Group 1 served as negative control. Groups 2-5 were administered 10% ethanol for six weeks. Group 3 was administered with extract (200 mg/kg), group 4 received the diet containing 10% ethanol plus a bolus of lactobacilli GG (1010 CFU), and group 5 animals were given silymarin along with alcohol and it served as positive control. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein content, γ-glutamyltransferase, glutathione S-transferase, oxidative stress markers, glutathione, malondialdehyde and glutathione reductase were determined using standard diagnostic kits. Histopathological analysis of liver tissue was also made. A positive relation was found between plasma endotoxin levels and degree of liver injury. The pathology records were also related positively with leukotriene B4 and thromboxane B2. But a negative correlation was obtained with PgE2 levels. This study led us to hypothesize that the increased endotoxin levels modulate liver metabolism of eicosanoid, which gradually leads to liver injury. Endotoxemia increases leukotriene and thromboxane levels in plasma.

Keywords: lactobacillus, Lichen rangiferinus, endotoxemia, silymarin

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7352 Effects of High Intensity Interval vs. Low Intensity Continuous Training on LXRβ, ABCG5 and ABCG8 Genes Expression in Male Wistar Rats

Authors: Sdiqeh Jalali, M. R. Khazdair

Abstract:

Liver X receptors (LXR) have an essential role in the regulation of cholesterol metabolism, and their activation increase ABCG5 and ABCG8 genes expression for the improvement of cholesterol excretion from the body during reverse cholesterol transport (RCT). The aim of this study was to investigate the effects of high-intensity interval (HIT) and low intensity continuous (LIT) trainings on gene expression of these substances after a high-fat diet in Wistar rats. Materials and Methods: Fifteen male Wistar rats were divided into 3 groups: control group (n = 5), HIT exercise group (n = 5) and LIT exercise group (n = 5). All groups used a high-fat diet for 13 weeks, and the HIT and LIT groups performed the specific training program. The expression of LXRβ, ABCG5, and ABCG8 genes was measured after the training period. Findings: Data analysis showed significantly higher levels of LXRβ, ABCG5, and ABCG8 gene expression in HIT and LIT groups compared to the control group (P ≤ 0.05). Conclusion: HIT and LIT trainings after a high-fat diet have beneficial effects on RCT that prevent heart attack. Also, HIT training may have a greater effect on cholesterol excretion during the reverse cholesterol transport mechanism than LIT.

Keywords: liver X receptor, atherosclerosis, interval training, endurance training

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