Search results for: old rats
Commenced in January 2007
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Paper Count: 734

Search results for: old rats

554 The Role Collagen VI Plays in Heart Failure: A Tale Untold

Authors: Summer Hassan, David Crossman

Abstract:

Myocardial fibrosis (MF) has been loosely defined as the process occurring in the pathological remodeling of the myocardium due to excessive production and deposition of extracellular matrix (ECM) proteins, including collagen. This reduces tissue compliance and accelerates progression to heart failure, as well as affecting the electrical properties of the myocytes resulting in arrhythmias. Microscopic interrogation of MF is key to understanding the molecular orchestrators of disease. It is well-established that recruitment and stimulation of myofibroblasts result in Collagen deposition and the resulting expansion in the ECM. Many types of Collagens have been identified and implicated in scarring of tissue. In a series of experiments conducted at our lab, we aim to elucidate the role collagen VI plays in the development of myocardial fibrosis and its direct impact on myocardial function. This was investigated through an animal experiment in Rats with Collagen VI knockout diseased and healthy animals as well as Collagen VI wild diseased and healthy rats. Echocardiogram assessments of these rats ensued at four-time points, followed by microscopic interrogation of the myocardium aiming to correlate the role collagen VI plays in myocardial function. Our results demonstrate a deterioration in cardiac function as represented by the ejection fraction in the knockout healthy and diseased rats. This elucidates a potential protective role that collagen-VI plays following a myocardial insult. Current work is dedicated to the microscopic characterisation of the fibrotic process in all rat groups, with the results to follow.

Keywords: heart failure, myocardial fibrosis, collagen, echocardiogram, confocal microscopy

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553 Genotoxic and Cytotoxic Effects of Salvia officinals Extracts on Rat Bone Marrow

Authors: Mohammed A. Alshehri

Abstract:

Salvia officinalis is an aromatic plant member of the mint (Labiatae) family. It is popular kitchen herb. Not surprise to find that the name of this herb related to cure, in Latin language Salvia means to cure where officinalis means medicinal which answer why the sage has a top place in the list of medicinal plants. The aim of the present study was to assess the genetic damage and cytological changes caused by exposure of the test organism (Rattusrattus) to Salvia officinals. For this purpose, adult female rats, weighing 200–250 g, were used as donors. A total of 36 adult Wister male rats were randomly assigned to five groups: the experimental groups (rats were intraperitonealy injected with Salvia officinalis pure extract at (0.1, 0.2, 0.5, 0.1mg/kg body weight, the same dose was administered once a day. Control group (rats were injected intraperitonealy physiological saline. And positive control were injected with Cyclophosphamide. On the 21st days following Salvia officinalis pure extract exposure, rats were sacrificed, and samples of bone marrow were collected. Following that, we performed a micronuclei (MN) test using MNNCE (Micro-nucleated normocromatic erythrocytes) and MNPCE (Micronucleated polychromatic erythrocytes), NDI (Nuclear division index), and cytological parameters using NDCI (nuclear division cytotoxicity index), necrotic, and apoptotic cells in rat's bone marrow samples. Results showed that there was a no significant increase in the frequency of micro-nucleatedas well as in cytological parameters in bone marrow cells. In light of these results, if Salvia officinalis pure extract may considered to be safe from the stand point of genotoxicity and cytotoxicity effects.

Keywords: Salvia officinalis, micronucleus, NDI, NDCI, toxicity, chromosomal aberrations

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552 Hepatoxicity induced Glyphosate-Based Herbicide Baron in albino rats

Authors: Manal E. A Elhalwagy, Nadia Amin Abdulmajeed, Hanan S. Alnahdi, Enas N. Danial

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Baron is herbicide includes (48% glyphosate) widely used in Egypt. The present study assesses the cytotoxic and genotoxic effect of baron on rats liver. Two groups of rats were treated orally with 1/10 LD 50, (275.49 mg kg -1) and 1/40 LD 50, (68.86 mg kg-1) glyphosate for 28 days compared with control group. Serum and liver tissues were taken at 14 and 28 days of treatment. An inhibition in Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were recorded at both treatment periods and reduction in total serum protein (TP) and albumin (ALB). However, non-significant changes in serum acetylcholinesterase (AChE). Elevation in oxidative stress biomarker malondyaldehyde (MDA) and the decline in detoxification biomarker total reduced glutathione (GSH), Glutathione S-transferase (GST) and superoxide dismutase (SOD) in liver tissues led to increase in percentage of DNA damage. Destruction in liver tissue architecture was observed . Although, Baron was classified in the safe category pesticides repeated exposure to small doses has great danger effect.

Keywords: glyphosate, liver toxicity, oxidative stress, DNA damage, commet assay

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551 Effect of Green Coffee Bean Extract on Gentamicin Induced Acute Renal Failure in Rats

Authors: Amina Unis, Samah S. El Basateeny, Noha A. H. Nassef

Abstract:

Introduction: Acute Renal Failure (ARF) is one of the most common problems encountered in hospitalized critically ill patients. In recent years great effort has been focused on the introduction of herbal medicine as a novel therapeutic agent for prevention of ARF. Hence, the current study was designed to investigate the effect of Green Coffee Bean Extract (GCBE) on gentamicin induced ARF in rats. Methods: The study was conducted on 60 male rats divided into six equal groups. Group 1 served as normal control group and GCBE was administered for 7 days at a dose of 20 mg/kg/day in group 2 and 40 mg/kg/day in group 3 to test the effect of GCBE on normal kidneys. ARF was induced by a daily intraperitoneal injection of gentamicin (80 mg/kg) for 7 days in group 4 (model group), group 5 (GCBE 20 mg/kg/day) and group 6 (GCBE 20 mg/kg/day). All rats were sacrificed after 7 days and blood was withdrawn for kidney function tests. Kidneys were removed for determination of renal oxidative stress markers and histopathological examination. Results: The present study showed that rats that received oral GCBE for 7 days without induction of ARF showed no significant change in all the assessed parameters in comparison to the normal control group, while rats in the groups that received oral GCBE for 7 days with induction of ARF showed a significant improvement in kidney functions tests (decrease in serum urea, serum creatinine, and blood urea nitrogen) when compared to the ARF model group. Moreover, there was significant amelioration in renal oxidative stress markers (renal malondialdehyde, renal superoxide dismutase) and renal histopathological changes in the GCBE treated groups along induction of ARF when compared to ARF model group. The most significant improvement was reported in the group where GCBE was administered for 7 days in a dose 40 mg/kg/day, along with induction of ARF. Conclusion: GCBE has a potential role in ameliorating renal damage involved in ARF mostly through its antioxidant effect.

Keywords: green coffee bean extract, gentamicin, acute renal failure, pharmacology

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550 The Impact of Co-Administration of Phosphodiesterase-5 Inhibitor and Sodium Selenite on Ischemia/Reperfusion Injury in a Rat Ovary Model: Biochemical and Histopathologic Evaluation

Authors: Waleed Aly Sayed Ahmed, Eman Kishk, Tahani Shams

Abstract:

Aim: To study the effects of co-administration of phosphodiesterase-5 inhibitor (PDE-5) and sodium selenite against the damage induced by ovarian ischemia-reperfusion in rats. Materials and Methods: A total of forty-two sexually mature, virgin, female rats were divided randomly into six groups of seven each: sham group (C), ischemia group (I), ischemia/reperfusion group (I/R), ischemia/reperfusion plus 1.4mg/kg sildenafil (I/R+S) group, ischemia/reperfusion plus 0.2mg/kg selenium (I/R+Se) group and ischemia/reperfusion plus combination of sildenafil and selenium (I/R+S+Se) group. In ischemia group (I), rats were exposed to ischemia for 3 hours (h). In ischemia/reperfusion group (I/R), rats were exposed to ischemia for 3 h followed by 6 h of reperfusion. Treated groups received 1.4mg/kg sildenafil or 0.2 mg/kg selenium or both 30 min before reperfusion. Both ovaries were surgically removed carefully. One ovary was examined for histopathological changes and the other was subject to biochemical analysis including malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx). Results: Assessment of ovarian tissue damage using a scoring system showed marked vascular congestion, interstitial edema, leukocyte infiltration, hemorrhage, and follicular degeneration in ischemia and ischemia/reperfusion groups. Tissue damage score for I, IR and all treated groups were significantly higher than those of the sham group (p<0.001), while tissue damage score decreased significantly in I/R+S and I/R+Se groups compared to I/R group (p<0.05), and notably, the difference was highly significant in I/R+S+Se group (p<0.001). There was significant increase in MDA levels and reduction in activities of CAT and GPx in I/R group compared to the sham group (p < 0.05). In I/R+S and I/R+Se groups, MDA was significantly decreased compared to the I/R group (p<0.05) and the difference was highly significant with co-administration of sildenafil and selenium (p<0.001). CAT and GPx were higher in all treated groups compared to I/R group (p<0.05). Conclusion: The co-administration of sildenafil citrate and selenium are highly protective against damage induced by ovarian ischemia/reperfusion in rats.

Keywords: phosphodiesterase-5 inhibitor, sildenafil, antioxidant, selenium, ovarian ischemia

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549 Effect of Post and Pre Induced Treatment with Hesperidin in N-Methyl N-Nitrosourea Induced Mammary Gland Cancer in Female Sprague-Dawley Rats

Authors: Vinay Kumar Theendra

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The main objective of the study is to evaluate the effectiveness of hesperidin in the treatment of breast cancer and causing less (or) no bone marrow depression which is the major side effect of the present anticancer drugs treating breast cancer, also to evaluate the mechanisms through which these compounds are exerting their effect. Breast cancer is induced by administering N-methyl N-Nitrosourea (MNU) at a dose of 50mg/kg body weight. Upon the termination of the experiment, the animals were sacrificed by the method of cervical dislocation. The animals were dissected along the ventral midline and were grossly examined for the presence of tumors. Then the tumours were removed along with the stroma. Vascular endothelial growth factor (VEGF) levels were estimated by using ELISA method. The first occurrence of palpable tumors was eight weeks after carcinogen treatment and the final tumour incidence was 100% in the MNU alone and topical treated rats. Whereas in rats of other treatment groups there is decreased tumour incidence which might be due to their antitumour activity. Hesperidin therapy inhibited angiogenesis which can be evident from the significant reduction in serum as well as tumour VEGF concentrations in comparison to the untreated mammary carcinoma bearing rats. Hesperidin is promising agents that exert direct antitumor and also antiangiogenic, antiproliferative and anti-inflammatory activities. Even though the potency is little lesser than standard drug vincristine, it has been proved to be safe without effecting haematological count.

Keywords: hesperidin, VEGF, COX 2, N-methyl N-nitrosourea

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548 Activity of Resveratrol on the Influence of Aflatoxin B1 on the Testes of Sprague Dawley Rats

Authors: Ali D. Omur, Betul Apaydin Yildirim, Yavuz S. Saglam, Selim Comakli, Mustafa Ozkaraca

Abstract:

Twenty-eight male Sprague Dawley rats (aged 3 months) were used in the study. The animals were given feed and water as ad libitum. Sprague Dawley rats were randomly divided into 4 groups as 7 rats in each group. Aflatoxin B1 (7.5 μg/200 g), resveratrol (60 mg/kg) was administered to rats in groups other than the control group. At the end of the 16th day, blood, semen and tissue specimens were taken by decapitation under ether anesthesia. The effects of aflatoxin B1 and resveratrol on spermatological, pathological and biochemical parameters were determined in rats. When we evaluate the spermatological parameters, it is understood that resveratrol has a statistically significant difference in terms of sperm motility and viability (membrane integrity) compared to the control group and aflatoxin B1 administration groups, indicating a protective effect on spermatological parameters (groups: control, resveratrol, aflatoxin B1 and Afb1 + res; respectively, values of motility: 71,42 ± 0,52b, 72,85 ± 1, 48c , 60,71 ± 1,30a, 57,14 ± 2, 40a; values of viability: 63,85 ± 1,33b, 70,42 ± 2,61c, 55,00 ± 1,54a, 56,57 ± 0,89a. In terms of pathological parameters -histopathological examination- in the control and resveratrol groups, seminiferous tubules were observed to be in normal structure. In the group treated with aflatoxin, the regular structure of the spermatogenic cells deteriorated, and the seminiferous tubules became necrotic and degenerative. In the group treated with Afb1 + res, the decreasing of necrotic and degenerative changes were determined compared with in the group treated with aflatoxin. As immunohistochemical examination, cleaved caspase 3 expression was found to be very low in the control and resveratrol groups. Cleaved caspase 3 expression was severely exacerbated in seminiferous tubules in aflatoxin group but cleaved caspase 3 expression level decreased in Afb1 + res. In the biochemical direction, resveratrol has been shown to inhibit the adverse effects of aflatoxin on antioxidant levels (GSH-mmol/L, CAT-kU/L, GPx-U/mL, SOD-EU/mL) and to show a protective effect. For this purpose, the use of resveratrol with antioxidant activity was investigated in preventing or ameliorating damage to aflatoxin B1. It has been concluded that resveratrol effectively prevents the aflatoxin-induced testicular damage and lipid peroxidation. It has also been shown that resveratrol has protective effects on sperm motility and viability.

Keywords: Aflatoxin B1, rat, resveratrol, sperm

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547 Hepatoprotective Effects of Parsley, Basil, and Chicory Aqueous Extracts against Dexamethasone-Induced in Experimental Rats

Authors: Hanan A. Soliman, Mohamed A. El-Desouky, Walaa G. Hozayen, Rasha R. Ahmed, Amal K . Khaliefa

Abstract:

Aim: The objective of this study is to investigate the hypoglycemic, hypolipidemic, and hepatoprotective effects of the aqueous extract of parsley, basil, and chicory whole plant in normal and dexamethasone (Dex) rats. Materials and Methods: 50 female albino rats were used in this study and divided into 5 groups (for each 10). Group (1) fed basal diet and maintained as negative control group. Group (2) received Dex in a dose of (0.1 mg/kg b. wt.). Groups 3, 4, and 5 were treated with Dex along with three different plant extracts of parsley, basil, and chicory (2 g/kg b. wt.), (400 mg/kg b. wt.), and (100 mg/kg b. wt.), respectively. Results: All these groups were treated given three times per week for 8 consecutive weeks. Dex-induced alterations in the levels of serum glucose, triglyceride, cholesterol, low-density lipoprotein-cholesterol levels and cardiovascular indices and serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities, liver thiobarbituric acid (TBARS) levels increased, while high-density lipoprotein-cholesterol, total protein, albumin, and liver glutathione (GSH) levels decreased. On the other hand, plant extracts succeeded to modulate these observed abnormalities resulting from Dex as indicated by the reduction of glucose, cholesterol, TBARS, and the pronounced improvement of the investigated biochemical and antioxidant parameters. Conclusions: It was concluded that probably, due to its antioxidant property, parsley, basil, and chicory extracts have hepatoprotective effects in Dex-induced in rats.

Keywords: antioxidants, dexamethasone, hyperglycemia, hyperlipidemia

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

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

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

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

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545 Blood Lipid Profile and Liver Lipid Peroxidation in Normal Rat Fed with Different Concentrations of Acacia senegal and Acacia seyal

Authors: Eqbal M. A. Dauqan, A. Aminah

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The aim of the present study was to evaluate the blood lipid profile and liver lipid peroxidation in normal rat fed with different concentrations of Acacia senegal and Acacia seyal. Thirty six Sprague Dawley male rats each weighing between 180-200g were randomly divided into two groups. Each group contains eighteen rats and were divided into three groups of 6 rats per group. The rats were fed ad libitum with commercial rat’s feed and tap water containing different concentrations of Acacia senegal and Acacia seyal (3% and 6%) for 4 weeks. The results at 4 weeks showed that there was no significant difference (p≤0.05) in the total cholesterol (TC) and triglycerides (TG) between the control group and treated groups while the results for the high density lipoprotein (HDL-C) showed a significant decrease (P≥0.05) at the 3% and 6% of gum arabic treated groups compared to control group. There was a significant increase (P≥0.05) in low density lipoprotein (LDL-C) with 3% and 6% of gum Arabic (GA) groups compared to the control group. The study indicated that there was no significant (p≤0.05) effect on TC and TG but there was significant effect (P≥0.05) on HDL-C and LDL-C in blood lipid profile of normal rat. The results showed that after 4 weeks of treatment the malondialdehyde (MDA) value in rat fed with 6% of A. seyal group was significantly higher (P≥0.05) than control or other treated groups of A. seyal and A. senegal studied. Thus, the two species of gum arabic did not have beneficial effect on blood lipid profile and lipid peroxidation.

Keywords: Acacia senegal, acacia seyal, lipid profile, lipid peroxidation, malondialdehyde (MDA)

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544 Effect of Jatropha curcas Leaf Extract on Castor Oil Induced Diarrhea in Albino Rats

Authors: Fatima U. Maigari, Musa Halilu, M. Maryam Umar, Rabiu Zainab

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Plants as therapeutic agents are used as drug in many parts of the world. Medicinal plants are mostly used in developing countries due to culture acceptability, belief or due to lack of easy access to primary health care services. Jatropha curcas is a plant from the Euphorbiaceae family which is widely used in Northern Nigeria as an anti-diarrheal agent. This study was conducted to determine the anti-diarrheal effect of the leaf extract on castor oil induced diarrhea in albino rats. The leaves of J. curcas were collected from Balanga Local government in Gombe State, north-eastern Nigeria; due to its bioavailability. The leaves were air-dried at room temperature and ground to powder. Phytochemical screening was done and different concentrations of the extract was prepared and administered to the different categories of experimental animals. From the results, aqueous leaf extract of Jatropha curcas at doses of 200mg/Kg and 400mg/Kg was found to reduce the mean stool score as compared to control rats, however, maximum reduction was achieved with the standard drug of Loperamide (5mg/Kg). Treatment of diarrhea with 200mg/Kg of the extract did not produce any significant decrease in stool fluid content but was found to be significant in those rats that were treated with 400mg/Kg of the extract at 2hours (0.05±0.02) and 4hours (0.01±0.01). A significant reduction of diarrhea in the experimental animals signifies it to possess some anti-diarrheal activity.

Keywords: anti-diarrhea, diarrhea, Jatropha curcas, loperamide

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543 Estimation of Human Absorbed Dose Using Compartmental Model

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

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Dosimetry is an indispensable and precious factor in patient treatment planning to minimize the absorbed dose in vital tissues. In this study, compartmental model was used in order to estimate the human absorbed dose of 177Lu-DOTATOC from the biodistribution data in wild type rats. For this purpose, 177Lu-DOTATOC was prepared under optimized conditions and its biodistribution was studied in male Syrian rats up to 168 h. Compartmental model was applied to mathematical description of the drug behaviour in tissue at different times. Dosimetric estimation of the complex was performed using radiation absorbed dose assessment resource (RADAR). The biodistribution data showed high accumulation in the adrenal and pancreas as the major expression sites for somatostatin receptor (SSTR). While kidneys as the major route of excretion receive 0.037 mSv/MBq, pancreas and adrenal also obtain 0.039 and 0.028 mSv/MBq. Due to the usage of this method, the points of accumulated activity data were enhanced, and further information of tissues uptake was collected that it will be followed by high (or improved) precision in dosimetric calculations.

Keywords: compartmental modeling, human absorbed dose, ¹⁷⁷Lu-DOTATOC, Syrian rats

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542 Preventive Effect of Zinc on Nickel Hepatotoxicity and Nephrotoxicity in Albino (Wistar) Rats

Authors: Zine Kechrid, Samira Bouhalit

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Aim: We studied the effect of intraperitonial zinc treatment on nickel sulphate-induced hepatotoxicity and nephrotoxicity in Wistar strain male albino rats. Materials and Methods: Liver and kidney dysfunction parameters represented by aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), blood glucose, serum total protein, serum urea, serum creatinine, and serum belurebin were estimated. Liver glutathione level, catalase and GPx activities were also determined in liver as indicators of oxidative damage. Result: Nickel treatment led to high serum glucose concentration and produced hepatotoxicity and nephrotoxicity characterized by increasing GPT, GOT and alkaline phosphatase activities, serum total protein, serum urea, serum creatinine and serum belurebin concentrations. In addition, liver glutathione level, catalase and GSH-Px activities diminished due to high lipid peroxidation. The simultaneous administration of zinc with nickel sulphate resulted in a remarkable improvement of the previous parameters compared with rats treated with nickel alone. Conclusion: In conclusion, nickel sulphate led to liver and kidney dysfunctions and hepatic lipid peroxidation in animals, but simultaneous treatment with zinc offers a relative protection against nickel induced hepatotoxicity, nephrotoxicity and lipid peroxidation.

Keywords: nickel, zinc, rats, GOT, GPT, nephrotoxicity, hepatotoxicity

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541 Evaluation of Anti-Arthritic Activity of Eulophia ochreata Lindl and Zingiber cassumunar Roxb in Freund's Complete Adjuvant Induced Arthritic Rat Model

Authors: Akshada Amit Koparde, Candrakant S. Magdum

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Objective: To investigate the anti-arthritic activity of chloroform extract and Isolate 1 of Eulophia ochreata Lindl and dichloromethane extract and Isolate 2 of Zingiber cassumunar Roxb in adjuvant arthritic (AA) rat model induced by Freund’s complete adjuvant (FCA). Methods: Forty two healthy albino rats were selected and randomly divided into six groups. Freund’s complete adjuvant (FCA) was used to induce arthritis and then treated with chloroform extract, isolate 1 and dichloromethane extract, isolate 2 for 28 days. The various parameters like paw volume, haematological parameters (RBC, WBC, Hb and ESR), were studied. Structural elucidation of active constituents isolate 1 and isolate 2 from Eulophia ochreata Lindl and Zingiber cassumunar Roxb will be done using GCMS and H1NMR. Results: In FCA induced arthritic rats, there was significant increase in rat paw volume whereas chloroform extract and Isolate 1 of Eulophia ochreata Lindl and dichloromethane extract and Isolate 2 of Zingiber cassumunar Roxb treated groups showed strong significant reduction in paw volume. The altered haematological parameters in the arthritic rats were significantly recovered to near normal by the treatment with extracts at the dose of 200 mg/kg. Further histopathological studies revealed the anti-arthritic activity of Eulophia ochreata Lindl and Zingiber cassumunar Roxb by preventing cartilage and bone destruction of the arthritic joints of AA rats. Conclusion: Extracts and isolates of Eulophia ochreata Lindl and Zingiber cassumunar Roxb have shown anti-arthritic activity. Decrease in paw volume and normalization of haematological abnormalities in adjuvant induced arthritic rats is significantly seen in the experiment. Further histopathological studies confirmed the anti-arthritic activity of Eulophia ochreata Lindl and Zingiber cassumunar Roxb.

Keywords: arthritis, Eulophia ochreata Lindl, Freund's complete adjuvant, paw volume, Zingiber cassumunar Roxb

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

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

Abstract:

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

Keywords: oxidative stress, mTOR, nitrosative stress, zymosan

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539 Protective Effects of Coenzyme Q10 and N-Acetylcysteine on Myocardial Oxidative Stress, Inflammation, and Impaired Energy metabolism in Carbon Tetrachloride Intoxicated Rats

Authors: Nayira A. Abd Elbaky, Amal J. Fatani, Hazar Yaqub, Nouf M. Al-Rasheed, Naglaa El-Orabi, Mai Osman

Abstract:

The present work is aimed to evaluate the protective effect of N-acetyl cystiene (NAC), coenzyme Q10 (CoQ10), and their combination against carbon tetrachloride (CCl4)-induced cardiotoxicity in rats. CCl4 treatment significantly elevated the levels of cardiac oxidative stress bio markers including nitric oxide (NO) and malondialdehyde (MDA). A concomitant decrease in the level of reduced glutathione and the activity of membrane bound enzyme, calcium-adenosine triphosphatase were observed in the hearts of rats exposed to CCl4 compared to respective values in normal group. Quantitative analysis of myocardial energy metabolism revealed a significant decrease in the glucose content coupled with depletion in the activities of myocardial glycolytic enzymes as hexokinase (HK), phosphofructokinase (PFK) and lactate dehydrogenase (LDH) after CCl4 treatment. In addition, a significant elevation in myocardial hydroxyproline level was observed in CCl4 intoxicated rats indicating interstitial collagen accumulation. Pretreatment with either NAC, CoQ10 or their combination successively alleviated the alterations in myocardial oxidative stress and antioxidant markers, as well as effectively up-regulated the decrease in cardiac energetic biomarkers in CCl4 intoxicated rats. Moreover, these antioxidants markedly reduced myocardial hydroxyproline level versus that of CCl4-treated animals. In conclusion, the present results illustrated that the prophylactic use of the current antioxidant resulted in a remarkable cardioprotective effect against CCl4 induced myocardial damage, which suggest that they may candidates as prophylactic agents against different cardio-toxins.

Keywords: carbon tetrachloride, lipid peroxidation, antioxidant, energy metabolism, hydroxyproline

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538 The Hypolipidemic and Anti-Nephrotoxic Potentials of Vernonia calvoana Extract in Acetaminophen-Treated Male Wistar Rats

Authors: Godwin E. Egbung, Item J. Atangwho, Diana O. Odey, Eyong U. Eyong

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Background of the study: The frequent abuse of acetaminophen by field workers in Calabar metropolis necessitated the present study on the hypolipidemic and anti-nephrotoxic potentials of Vernonia calvoana (VC) extract in acetaminophen (paracetamol) treated male albino Wistar rats Methods:. Thirty-five (35) male albino Wistar rats weighing 100-150 g were divided into five (5) groups of seven rats each. Group 1 served as normal control, group 2 received normal saline after treatment with Acetaminophen (PCM), group 3 was treated with VC extracts (200 mg/kg body weight), group 4 received VC extracts ( 400 mg/kg body weight) and group 5 was administered 100 mg/kg body weight of Vitamin E. At the end of the 21 days treatment period, the animals were sacrificed using chloroform vapours, and blood was collected via cardiac puncture and used for analyses of haematological as well as biochemical indices. Results: Results indicated significant decreases (p < 0.001) in LDL-c, TC and TG levels in groups 3,4 and 5 relative to both the control as well as group 2, the atherogenic index showed a significant decrease at p < 0.001) in all treated groups compared with control and PCM- treated group. However, both extracts treated groups and vitamin E treated group showed significant (p < 0.001) increase in HDL-c relative to the control and PCM treated group. Serum potassium concentration was significantly (p < 0.05 and 0.001) reduced across all the treated groups compared with control and PCM- treated groups. Group 4 showed significant (p < 0.001) increase in RBC count, Hb, and PCV compared with PCM- treated group. Conclusions: We therefore conclude that ethanolic leaf extract of VC possesses probable anti-anemic, hypolipidemic potentials, and also ameliorates serum electrolyte imbalance in paracetamol- induced toxicity.

Keywords: acetaminophen, haematological indices, hypolipidemic potentials, serum lipid profile, vernonia calvoana, wistar rats

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537 Comparison of Gestational Diabetes Influence on the Ultrastructure of Rectus Abdominis Muscle in Women and Rats

Authors: Giovana Vesentini, Fernanda Piculo, Gabriela Marini, Debora Damasceno, Angelica Barbosa, Selma Martheus, Marilza Rudge

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Problem statement: Skeletal muscle is highly adaptable, muscle fiber composition and size can respond to a variety of stimuli, such physiologic, as pregnancy, and metabolic abnormalities, as Diabetes mellitus. This study aimed to analyze the effects of pregnancy-associated diabetes on the rectus abdominis muscle (RA), and to compare this changes in rats and women. Methods: Female Wistar rats were maintained under controlled conditions and distributed in Pregnant (P) and Long-term mild pregnant diabetic (LTMd) (n=3 r/group). Diabetes in rats was induced by streptozotocin (100mg/Kg, sc) on the first day of life, for a hyperglycemic state between 120-300 mg/dL in adult life. Female rats were mated overnight, at day 21 of pregnancy were anesthetized, and killed for the harvesting of maternal RA. Pregnant women who attended the Diabetes Prenatal Care Clinic of Botucatu Medical School were distributed in Pregnant non-diabetic (Pnd) and Gestational Diabetic (GDM) (n=3 w/group). The diagnosis of GDM was established according to ADA’s criteria (2016). The harvesting of RA was during the cesarean section. Transversal cross-sections of the RA of both women and rats were analyzed by transmission electron microscopy. All procedures were approved by the Ethics Committee on Animal Experiments of the Botucatu Medical School (Protocol Number 1003/2013) and by the Botucatu Medical School Ethical Committee for Human Research in Medical Sciences (CAAE: 41570815.0.0000.5411). Results: The photomicrographs of the RA of rats revealed disorganized Z lines, thinning sarcomeres, and a usual quantity of intermyofibrillar mitochondria in the P group. The LTMd group showed swollen sarcoplasmic reticulum, dilated T tubes and areas with sarcomere disruption. The ultrastructural analysis of Pnd non-diabetic women in the RA showed well-organized myofibrils forming intact sarcomeres, organized Z lines and a normal distribution of intermyofibrillar mitochondria. The GDM group revealed increase in intermyofibrillar mitochondria, areas with sarcomere disruption and increased lipid droplets. Conclusion: Pregnancy and diabetes induce adaptations in the ultrastructure of the rectus abdominis muscle for both women and rats, changing the architectural design of these tissues. However, in rats these changes are more severe maybe because, besides the high blood glucose levels, the quadrupedal animal may suffer an excessive mechanical tension during pregnancy by gravity. Probably, these findings may suggest that these alterations are a risk factor that contributes to the development of muscle dysfunction in women with GDM and may motivate treatment strategies in these patients.

Keywords: gestational diabetes, muscle dysfunction, pregnancy, rectus abdominis

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536 Hepatoprotective Activity of Ethanolic Extract of Terminalia paniculata against Anti-Tubercular Drugs (ATT) Induced Hepatotoxicity in Wistar Albino Rats

Authors: Mohana Babu Amberkar, Meena Kumari K, Ravi, Arjun, Christopher Rockson

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The aim of this research is to evaluate the hepatoprotective activity of Terminalia paniculata (Tp) against ATT induced hepatic damage in rats.Three hepatotoxic ATT drugs Isoniazid + Rifampicin + Pyrazinamide, silymarin as standard hepatoprotective drug and 0.5% carboxymethylcellulose (CMC) as a control were used. Tp extract and silymarin were administered orally with ATT drugs for 90 days. Two doses 250 and 500 mg/kg of Tp extract, ATT drugs and silymarin were administered as suspensions with 0.5% CMC. ATT treated rats showed a significant increase in aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and lipid peroxides in the serum vs. control. Treatment of silymarin and Tp (250mg/kg) extract showed hepatoprotective activity against the hepatic damage by ATT. This was evident from significant reduction in serum liver enzymes levels, and also there was a significant increase in serum proteins, albumin and total liver tissue thiols as compared to the ATT treated groups. Tp was found to possess hepatoprotective property.

Keywords: antitubercular drugs, hepatoprotective, liver enzymes, Terminalia paniculata

Procedia PDF Downloads 441
535 The Combined Effect of Different Levels of Fe(III) in Diet and Cr(III) Supplementation on the Ca Status in Wistar

Authors: Staniek Halina

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The inappropriate trace elements supply such as iron(III) and chromium(III) may be risk factors of many metabolic disorders (e.g., anemia, diabetes, as well cause toxic effect). However, little is known about their mutual interactions and their impact on these disturbances. The effects of Cr(III) supplementation with a deficit or excess supply of Fe(III) in vivo conditions are not known yet. The objective of the study was to investigate the combined effect of different Fe(III) levels in the diet and simultaneous Cr(III) supplementation on the Ca distribution in organs in healthy rats. The assessment was based on a two-factor (2x3) experiment carried out on 54 female Wistar rats (Rattus norvegicus). The animals were randomly divided into 9 groups and for 6 weeks, they were fed semi-purified diets AIN-93 with three different Fe(III) levels in the diet as a factor A [control (C) 45 mg/kg (100% Recommended Daily Allowance for rodents), deficient (D) 5 mg/kg (10% RDA), and oversupply (H) 180 mg/kg (400% RDA)]. The second factor (B) was the simultaneous dietary supplementation with Cr(III) at doses of 1, 50 and 500 mg/kg of the diet. Iron(III) citrate was the source of Fe(III). The complex of Cr(III) with propionic acid, also called Cr₃ or chromium(III) propionate (CrProp), was used as a source of Cr(III) in the diet. The Ca content of analysed samples (liver, kidneys, spleen, heart, and femur) was determined with the Atomic Absorption Spectrometry (AAS) method. It was found that different dietary Fe(III) supply as well as Cr(III) supplementation independently and in combination influenced Ca metabolism in healthy rats. Regardless of the supplementation of Cr(III), the oversupply of Fe(III) (180 mg/kg) decreased the Ca content in the liver and kidneys, while it increased the Ca saturation of bone tissue. High Cr(III) doses lowered the hepatic Ca content. Moreover, it tended to decrease the Ca content in the kidneys and heart, but this effect was not statistically significant. The combined effect of the experimental factors on the Ca content in the liver and the femur was observed. With the increase in the Fe(III) content in the diet, there was a decrease in the Ca level in the liver and an increase in bone saturation, and the additional Cr(III) supplementation intensified those effects. The study proved that the different Fe(III) content in the diet, independently and in combination with Cr(III) supplementation, affected the Ca distribution in organisms of healthy rats.

Keywords: calcium, chromium(III), iron(III), rats, supplementation

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534 Study on the Effect Cabbage (Brassica oleracea) and Ginger (Zingiber officinale) Extracts on Rat Liver Injuries Induced by Carbon tetrachloride (CCl4)

Authors: Asmaa F. Hamouda, Randa M Shrourou

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Cabbage (Brassica oleracea) and Ginger (Zingiber officinale) constitute apportion of regular human diet. The effect of Cabbage(CE) and Ginger extracts(GE) separately on liver nitric oxide (NO), malondialdehyde (MDA), as well as serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, total cholesterol(TC), triglyceride(T.G), high density lipoprotein(HDL cholesterol), low density lipoprotein (LDL cholesterol), thyroid-stimulating hormone (TSH), Triiodothyronine (T3), Thyroxine (T4) in rats treated and untreated with carbon tetrachloride (CCl4) was studied. The levels of NO, MDA, as well as serum AST, ALT, total bilirubin, TC, T.G, LDLand TSH showed an elevation and decline in HDL, T3, and T4 in rats treated with CCl4 as compared to control. Treatment of rats with GE pre, during, and post CCl4 administration improved NO, MDA, as well as serum AST, ALT, total bilirubin, TC, T.G, HDL, LDL, TSH, T3, T4 as compared to CCl4, indicates that GE improve thyroid function and reduced oxidative stress as well as injuries induced by CCl4. Treatment of rats with CE pre, during, and post CCl4 administration did not improved in the thyroid hormones and lipid profile levels as compared to CCl4. These findings suggest that ginger treatment exerts a protective effect on metabolic disorders by decreasing oxidative stress.

Keywords: liver injuries, carbon tetrachloride (CCl4), cabbage (Brassica oleracea), ginger (Zingiber officinale), thyroid function

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533 Nephroprotective Effect of Asparagus falcatus Leaf Extract on Adriamycin Induced Nephrotoxicity in Wistar Rats: A Dose Response Study

Authors: A. M. S. S. Amarasiri, A. P. Attanayake, K. A. P. W. Jayatilaka, L. K. B. Mudduwa

Abstract:

Adriamycin (ADR) is an effective anthracyclin antitumor drug, but its clinical use is limited due to renal toxicity. The leaves of Asparagus falcatus (Family: Liliaceae) have been used in the management of renal diseases since antiquity. In the present investigation, the aqueous leaf extract of A. falcatus was evaluated for acute nephroprotective activity in ADR induced nephrotoxic rats. Nephrotoxicity was induced in healthy male Wistar rats by intraperitoneal administration of ADR 20 mg/kg. The lyophilized powder of the aqueous refluxed (4h) leaf extract of A. falcatus was administered orally at three selected doses; 200, 400 and 600 mg/kg for three consecutive days. Fosinopril sodium (0.09 mg/kg) was used as the standard drug. Administration of the plant extract and the standard drug was commenced 24 hours after the induction of nephrotoxicity to rats. The nephroprotective effect was determined by selected biochemical parameters and by the assessment of histopathology on H and E stained kidney sections. The results were compared to a group of control rats with ADR induced nephrotoxicity. A group of rats administered with the equivalent volume of normal saline served as the healthy control. Administration of ADR 20 mg/kg produced a significant increase in the concentrations of serum creatinine (61%) and urine protein (73%) followed by a significant decrease in serum total protein (21%) and albumin (44%) of the plant extract treated animals compared to the healthy control group (p < 0.05). The aqueous extract of Asparagus falcatus at the three doses; 200, 400 and 600 mg/kg and the standard drug were found to decrease the elevation of concentrations of serum creatinine (33%, 51%, 54% and 42%) and urine protein (8%, 63%, 80% and 86%) respectively. The serum concentrations of total protein (12%, 17%, 29% and 12%) and albumin (3%, 17%, 17% and 16%) were significantly increased compared to the nephrotoxic control group respectively. Assessment of histopathology on H and E stained kidney sections demonstrated that ADR induced renal injury, as evidenced by loss of brush border, cytoplasmic vacuolization, pyknosis in renal tubular epithelial cells, haemorrhages, glomerular congestion and presence of hyaline casts. Treatment with the plant extract and the standard drug resulted in attenuation of the morphological destruction in rats. The results of the present study revealed that the aqueous leaf extract of A. falcatus possesses significant nephroprotective activity against adriamycin induced acute nephrotoxicity. The improved kidney functions were supported with the results of selected biochemical parameters and histological changes observed on H and E stained sections of the kidney tissues in Wistar rats.

Keywords: adriamycin induced nephrotoxicity, asparagus falcatus, biochemical assessment, histopathological assessment, nephroprotective activity

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532 Acute Antihyperglycemic Activity of a Selected Medicinal Plant Extract Mixture in Streptozotocin Induced Diabetic Rats

Authors: D. S. N. K. Liyanagamage, V. Karunaratne, A. P. Attanayake, S. Jayasinghe

Abstract:

Diabetes mellitus is an ever increasing global health problem which causes disability and untimely death. Current treatments using synthetic drugs have caused numerous adverse effects as well as complications, leading research efforts in search of safe and effective alternative treatments for diabetes mellitus. Even though there are traditional Ayurvedic remedies which are effective, due to a lack of scientific exploration, they have not been proven to be beneficial for common use. Hence the aim of this study is to evaluate the traditional remedy made of mixture of plant components, namely leaves of Murraya koenigii L. Spreng (Rutaceae), cloves of Allium sativum L. (Amaryllidaceae), fruits of Garcinia queasita Pierre (Clusiaceae) and seeds of Piper nigrum L. (Piperaceae) used for the treatment of diabetes. We report herein the preliminary results for the in vivo study of the anti-hyperglycaemic activity of the extracts of the above plant mixture in Wistar rats. A mixture made out of equal weights (100 g) of the above mentioned medicinal plant parts were extracted into cold water, hot water (3 h reflux) and water: acetone mixture (1:1) separately. Male wistar rats were divided into six groups that received different treatments. Diabetes mellitus was induced by intraperitoneal administration of streptozotocin at a dose of 70 mg/ kg in male Wistar rats in group two, three, four, five and six. Group one (N=6) served as the healthy untreated and group two (N=6) served as diabetic untreated control and both groups received distilled water. Cold water, hot water, and water: acetone plant extracts were orally administered in diabetic rats in groups three, four and five, respectively at different doses of 0.5 g/kg (n=6), 1.0 g/kg(n=6) and 1.5 g/kg(n=6) for each group. Glibenclamide (0.5 mg/kg) was administered to diabetic rats in group six (N=6) served as the positive control. The acute anti-hyperglycemic effect was evaluated over a four hour period using the total area under the curve (TAUC) method. The results of the test group of rats were compared with the diabetic untreated control. The TAUC of healthy and diabetic rats were 23.16 ±2.5 mmol/L.h and 58.31±3.0 mmol/L.h, respectively. A significant dose dependent improvement in acute anti-hyperglycaemic activity was observed in water: acetone extract (25%), hot water extract ( 20 %), and cold water extract (15 %) compared to the diabetic untreated control rats in terms of glucose tolerance (P < 0.05). Therefore, the results suggest that the plant mixture has a potent antihyperglycemic effect and thus validating their used in Ayurvedic medicine for the management of diabetes mellitus. Future studies will be focused on the determination of the long term in vivo anti-diabetic mechanisms and isolation of bioactive compounds responsible for the anti-diabetic activity.

Keywords: acute antihyperglycemic activity, herbal mixture, oral glucose tolerance test, Sri Lankan medicinal plant extracts

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531 Feasibility of Phenolic Acids Rich Fraction from Gynura procumbens as Potential Antihyperlipidemic Agent

Authors: Vikneswaran Murugaiyah, Sultan Ayesh Mohammed Saghir, Kisantini Murugesu, Mohd. Zaini Asmawi, Amirin Sadikun

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Gynura procumbens is a popular medicinal plant used as a folk medicine in Southeast Asia to treat kidney diseases, diabetes mellitus and hyperlipidemia. The present study aims to investigate the antihyperlipidemic potential of phenolic acids rich fraction (PARF) from G. procumbens in chemically-induced acute and high fat diet-induced chronic hyperlipidemic rats. Ethanolic extract of G. procumbens leaves exhibited significant reductions in total cholesterol (TC) and triglycerides (TG) levels (P < 0.01 and P < 0.001, respectively) of poloxamer 407-induced rats compared to hyperlipidemic control after 58 h of treatment. Upon bioactivity guided fractionation the antihyperlipidemic activity was found to be concentrated in the PARF, which significantly reduced the TC and TG levels (P < 0.001). HPLC analysis revealed that 3,5-dicaffeoylquinic acid; 4,5-dicaffeoylquinic acid and chlorogenic acid are the major compounds in the PARF. Likewise, chlorogenic acid (60 mg/kg) exhibited significant reductions in TC and TG levels of hyperlipidemic rats (P < 0.001). Both chlorogenic acid and PARF significantly reduced LDL, VLDL and atherogenic index (P<0.01), while PARF increased the HDL (P < 0.01) compared to hyperlipidemic control. Both were found to be not cytotoxic against normal and cancer cell lines. In addition, LD50 of orally administered PARF was more than 5,000 mg/kg. Further investigation in high fat diet-induced chronic hyperlipidemic rats revealed that chronic administration of PARF dose-dependently restored the increase in lipids parameters. In summary, the phenolic acids rich fraction of G. procumbens leaves showed promising antihyperlipidemic effect in both chemically- and diet-induced hyperlipidemic rats that warrants further elucidation on its mechanisms of action.

Keywords: Antihyperlipidemic, Gynura procumbens, phenolic acids, chlorogenic acid, poloxamer-407, high fat diet

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530 Raw Japanese Quail Egg Produces Analgesic, Anti-Inflammatory and Gastro-Protective Effects in Rats

Authors: Sani Ismaila, Shafiu Yau, Abubakar Salisu, Buhari Salisu, Sharifat Balogun, Mustapha Abubakar, Biobaku Khalid, Agaie Bello

Abstract:

Over the years, Japanese quail egg has been in use in the management of diseases. The objective of this study was to evaluate the analgesic, anti-inflammatory and gastroprotective effects of raw Quail egg (yolk + albumin) in rats. Pain was assessed in rats by recording the latent period and writing reflex, anti-inflammatory effect was determined using both motility and compression test, while the gastro-protective effects were assessed by observing the histology of the stomach after diclofenac-induced gastric ulcers and subsequent treatment with the quail egg, Rats were randomly assigned into 4 groups; Groups I: were the control non-treated (NT), Group II were treated with Tramadol 50 mg/kg/Os (TMD) or Indomethacin (IND) 5mg/kg/Os (positive control for the writhing reflex determination), while group III and IV were treated with 3 and 6g/kg of raw quail egg respectively). Groups treated with quail egg in both doses showed a significant increase in the latent period (p <0 .05) when compared to the control NT, but lower than the group treated with tramadol at 20mins interval (p<0.05). Writing reflexes decrease in groups II, III, and IV compared to the NT group (p < 0.05). While motility increases significantly (p < 0.05) in groups II, compared to I (p<0.05). Control non-treated rats showed a quicker and extensive response to compression using the Vanier calliper on the inflamed paw compared to groups II-IV (p < 0.05). Histological studies of the stomach revealed sloughing of the epithelia, cellular infiltration with micro abscesses in the non-treated, while groups treated concurrently with quail egg showed proliferation of the glandular epithelia and goblet cells, and those treated 30 minutes before diclofenac administration showed proliferation of glands and thickening of the squamous epithelia. This study showed that quail egg has analgesic, anti-inflammatory and gastro-protective potentials and can be used as adjuvant treatment whenever COX-2 enzymes inhibitors are indicated.

Keywords: analgesia, anti-inflammatory, gastroprotective effect, japanese quail egg

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529 Investigation of Ezetimibe Administration on Cell Survival Markers in Kidney Ischemia

Authors: Zahra Heydari

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Introduction: One of the major clinical issues is acute renal failure, which is caused by ischemia-reperfusion of the kidney and is associated with high mortality. Despite advances in this area, important issues such as tissue necrosis, cell apoptosis, and so on in damaged tissue are suggestive for more researches and study on this subject. Objective: Evaluation of the potential utility of Ezetimibe in reducing injuries and cell death induced by kidney ischemia/ reperfusion through inducing expression changes of different cellular pathways in adult Sprague-Dawley rats. Materials and methods: Forty rats weighing 180-200g were divided into 4 groups. For this purpose, the first right kidneys of the rats were removed during surgery. After 20 days, the left renal artery was closed with a soft clamp and reperfusion was performed. After 24 hours, blood samples were collected and sent to the laboratory with kidneys to measure bax and bcl-2 by Western blotting and histopathological tests. Results: Quantitative damage reviews of Kidney tissue indicates damage Acute and severe tubular lesions were observed in the ischemia group. Also, the amount of injury was significantly reduced in the treatment group. There was also a significant difference between the ischemia and sham groups. In general, the results show that a single dose of 1.2 mg/kg of ezetimibe can reduce the bax/ bcl-2 ratio compared to the ischemia group. In general, the results showed Ezetimibe is effective in reducing cell damage and death due to ischemia/ reperfusion after renal ischemia through changes in the expression of various cellular pathways in rats.

Keywords: acute renal failure, renal ischemia-reperfusion injury, ezetimibe, apoptosis

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528 Anti-Arthritic Effect of a Herbal Diet Formula Comprising Fruits of Rosa Multiflora and Flowers of Lonicera Japonica

Authors: Brian Chi Yan Cheng, Hui Guo, Tao Su, Xiu‐qiong Fu, Ting Li, Zhi‐ling Yu

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Rheumatoid arthritis (RA) affects around 1% of the globe population. Yet, there is still no cure for RA. Toll-like receptor 4 (TLR4) signalling has been found to be involved in the pathogenesis of RA, making it a potential therapeutic target for RA treatment. A herbal formula (RL) consisting of fruits of Rosa Multiflora (Eijitsu rose) and flowers of Lonicera Japonica (Japanese honeysuckle) has been used in treating various inflammatory disorders for more than a thousand year. Both of them are rich sources of nutrients and bioactive phytochemicals, which can be used in producing different food products and supplements. In this study, we would evaluate the anti-arthritic effect of RL on collagen-induced arthritis (CIA) in rats and investigate the involvement of TLR4 signaling in the mode of action of RL. Anti-arthritic efficacy was evaluated using CIA rats induced by bovine type II collagen. The treatment groups were treated with RL (82.5, 165, and 330 mg/kg bw per day, p.o.) or positive control indomethacin (0.25 mg/kg bw per day, p.o.) for 35 days. Clinical signs (hind paw volume and arthritis severity scores), changes in serum inflammatory mediators, pro-/antioxidant status, histological and radiographic changes of joints were investigated. Spleens and peritoneal macrophages were used to determine the effects of RL on innate and adaptive immune responses in CIA rats. The involvement of TLR4 signalling pathways in the anti-arthritic effect of RL was examined in cartilage tissue of CIA rats, murine RAW264.7 macrophages and human THP-1 monocytic cells. The severity of arthritis in the CIA rats was significantly attenuated by RL. Antioxidant status, histological score and radiographic score were efficiently improved by RL. RL could also dose-dependently inhibit pro-inflammatory cytokines in serum of CIA rats. RL significantly inhibited the production of various pro-inflammatory mediators, the expression and/or activity of the components of TLR4 signalling pathways in animal tissue and cell lines. RL possesses anti-arthritic effect on collagen-induced arthritis in rats. The therapeutic effect of RL may be related to its inhibition on pro-inflammatory cytokines in serum. The inhibition of the TAK1/NF-κB and TAK1/MAPK pathways participate in the anti-arthritic effects of RL. This provides a pharmacological justification for the dietary use of RL in the control of various arthritic diseases. Further investigation should be done to develop RL into a anti-arthritic food products and/or supplements.

Keywords: japanese honeysuckle, rheumatoid arthritis, rosa multiflora, rosehip

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527 Gastro-Protective Actions of Melatonin and Murraya koenigii Leaf Extract Combination in Piroxicam Treated Male Wistar Rats

Authors: Syed Benazir Firdaus, Debosree Ghosh, Aindrila Chattyopadhyay, Kuladip Jana, Debasish Bandyopadhyay

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Gastro-toxic effect of piroxicam, a classical non-steroidal anti-inflammatory drug (NSAID), has restricted its use in arthritis and similar diseases. The present study aims to find if a combination of melatonin and Murraya koenigii leaf extract therapy can protect against piroxicam induced ulcerative damage in rats. For this study, rats were divided into four groups namely control group where rats were orally administered distilled water, only combination treated group, piroxicam treated group and combination pre-administered piroxicam treated group. Each group of rats consisted of six animals. Melatonin at a dose of 20mg/kg body weight and antioxidant rich Murraya koenigii leaf extract at a dose of 50 mg /kg body weight were successively administered at 30 minutes interval one hour before oral administration of piroxicam at a dose of 30 mg/kg body weight to Wistar rats in the combination pre-administered piroxicam treated group. The rats of the animal group which was only combination treated were administered both the drugs respectively without piroxicam treatment whereas the piroxicam treated animal group was administered only piroxicam at 30mg/kg body weight without any pre-treatment with the combination. Macroscopic examination along with histo-pathological study of gastric tissue using haemotoxylin-eosin staining and alcian blue dye staining showed protection of the gastric mucosa in the combination pre-administered piroxicam treated group. Determination of adherent mucus content biochemically and collagen content through Image J analysis of picro-sirius stained sections of rat gastric tissue also revealed protective effects of the combination in piroxicam mediated toxicity. Gelatinolytic activity of piroxicam was significantly reduced by pre-administration of the drugs which was well exhibited by the gelatin zymography study of the rat gastric tissue. Mean ulcer index determined from macroscopic study of rat stomach reduced to a minimum (0±0.00; Mean ± Standard error of mean and number of animals in the group=6) indicating the absence of ulcer spots on pre-treatment of rats with the combination. Gastro-friendly prostaglandin (PGE2) which otherwise gets depleted on piroxicam treatment was also well protected when the combination was pre-administered in the rats prior to piroxicam treatment. The requirement of the individual drugs in low doses in this combinatorial therapeutic approach will possibly minimize the cost of therapy as well as it will eliminate the possibility of any pro-oxidant side effects on the use of high doses of antioxidants. Beneficial activity of this combination therapy in the rat model raises the possibility that similar protective actions might be also observed if it is adopted by patients consuming NSAIDs like piroxicam. However, the introduction of any such therapeutic approach is subject to future studies in human.

Keywords: gastro-protective action, melatonin, Murraya koenigii leaf extract, piroxicam

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526 Effect of Insulin versus Green Tea on the Parotid Gland of Streptozotocin Induced Diabetic Rats

Authors: H. El-Messiry, M. El-Zainy, D. Ghazy

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Diabetes is a metabolic disease that results in a variety of oral health complications. Green tea is a natural antioxidant proved to have powerful effects against diabetes. The aim of this study was to compare between the effect of insulin and green tea on the Parotid gland of streptozotocin induced diabetic Albino rats by using light and transmission electron microscopy. Forty male Albino rats were divided into control group and diabetic groups. The diabetic group received a single injection of 40 mg/kg of streptozotocin intra-peritoneal under anesthesia and was further subdivided into three subgroups: The diabetic untreated subgroup which was untreated for two weeks, the insulin treated subgroup which has received insulin subcutaneously in a daily dose of 5 IU/kg body weight/day for two weeks and a green tea treated subgroup received a daily dose of 1 ml/ 100 gm body weight intragastrically for two weeks. Rats were terminated and parotid glands were dissected and processed for light and transmission electron microscopic examination. Histological examination of the diabetic untreated subgroup revealed acinar cells with pyknotic and hyperchromatic nuclei with cytoplasmic vacuolations. Ultrastructurally, acinar cells showed nuclear pleomorphism, dilated rough endoplasmic reticulum and swollen mitochondria with damaged cristae. Inflammatory cell infiltration was detected both histologically and ultrastructurally. Ducts showed signs of degeneration with loss of their normal outline and stagnated secretion within the lumen. However, insulin and green tea treated subgroups showed minimal degenerative damage and were almost similar to the control with minimal changes. Treatment of the parotid gland of the streptozotocin induced diabetic rats with GT was closely comparable to the traditional insulin therapy in reducing signs of histological and ultrastructural damage.

Keywords: diabetes, green tea, insulin, parotid

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525 Effects of Achillea millefolium L. Extract on Rat Spermatogenesis

Authors: Nasrin Takzaree, Gholamreza Hassanzadeh, Abbas Hadjiakhoondi, Mohammadreza Rouini

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Introduction: Today herbal medicine are extensively used for various therapeutic reasons. Whereas Achillea millefolium L. comprises different chemical compounds it is used in classic and modern medicine for different purposes. Concerning the family planning as a principle matter, the idea of using specific herbal medicine is of great importance. Purpose: To investigate the effects of Achillea millefolium L. extract on fertility power and spermatogenesis process in male mature Wistar rats and the anti-fertility effects of this extract in male genital system. Material and methods: In this study 32 male mature Wistar rats were randomly divided in to 4 experimental groups. 1st experimental group included 8 rats receiving Achillea millefolium extract at the dose of 200 mg/kg intraperitoneally. Second and third groups received the extract the same at the doses of 400 and 800 mg/kg respectively. 4th group was considered as control group in which the parenteral distilled water was administered. after 20 days, rats were sacrificed and the spermatogenesis process was histologically examined. Results: In experimental groups receiving high doses of extract comparing with control group, thickness in seminiferous tubules basal membrane, decrease in germinal epithelium cells, congestion in testicular tissue, disarrangement in germinal epithelium cells as well as decrease in cellular condense were observed (p<0.001). Conclusion: Findings suggest that alcoholic extract of Achillea millefolium at high concentrations lead to the structural alterations and changes in spermatogenesis in testicular tissue.

Keywords: spermatogenesis, alcoholic extract of Achillea millefolium L., testis, Wistar rat

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