Experimental therapeutic intervention with alpha tocopherol in ethanol induced testicular injuries in rats

Infertility is well-established harmful effect in chronic alcoholism and so far, there is no effective treatment for this condition. The study was conducted to determine the effects of alpha tocopherol on ethanol induced testicular injuries in male albino rats of Wistar strain. Five groups (n=6) of animals were used. Group I served as control. Group II received daily 1.6g ethanol/kg body weight/day for 4 weeks orally. Group III received 1.6g ethanol+80mg alpha tocopherol/kg body weight/day for four weeks orally. Group IV received 1.6g ethanol/kg body weight for/day 4 weeks and followed by 80mg alpha tocopherol/kg body weight/day for four weeks orally. Group V received 1.6g ethanol/kg body weight/day orally for 4 weeks, followed by 4 weeks abstinence. Twently-four hours after the last treatment the rats were sacrificed using anesthetic ether. Testes were removed and used for the estimation of extent of lipid peroxidation and tissue levels of antioxidants and steroidogenic enzymes. Alpha tocopherol treatment increased the activities of testicularΔ ⁵, 3β-HSD. Moreover, the treatment was also associated with significant decrease in testicular oxidative stress. Ethanol-induced oxidative stress and decreased steroidogenesis can be reversed by treatment with alpha tocopherol.     

Role of oxidative stress in ethanol induced germ cell apoptosis — An experimental study in rats

The study was undertaken to evaluate the possible involvement of oxidative stress in the pathogenesis of ethanol induced testicular atrophy in rats. Adult male rats were orally administered ethanol at a dose of 1.6 g/kg body weight/day for four weeks. Twenty-four hours after the last treatment the rats were sacrificed using anesthetic ether. Testes were removed and weighed. Apoptosis was studied by using the Feulgen reaction on 5 μ thin paraffin sections of testis. Testicular homogenate was prepared and centrifuged. The supernatant was used for the estimation of extent of lipid peroxidation and antioxidant defense status. There was significant reduction in body weight: and in testicular weight and diameter in ethanol treated rats. Extent of germ cell apoptosis was significantly high in ethanol treated rats. Ethanol treated rats showed significantly high tissue TBARS level and glutathione S-transferase activity; and low tissue ascorbic acid, reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities. Chronic ethanol administration resulted in high oxidative stress in the testes either due to increased extent of lipid peroxidation or due to decreased antioxidant defenses, and thereby induces germ cell apoptosis leading to testicular atrophy.     

Effect of ethanol on liver antioxidant defense systems: Adose dependent study

Alcohol induced oxidative stress is linked to the metabolism of ethanol. In this study it has been observed that administration of ethanol in lower concentration caused gain in body and liver weight. while higher concentration of ethanol caused lesser gain in body and liver weight. Ethanol treatment enhanced lipid peroxidation significantly, depletion in levels of hepatic glutathione and ascorbate, accompanied by a decline in the activities of glutathione peroxidase and glutathione reductase, and increased in hepatic glutathione s-transferase activity. Interestingly catalase activity increases in lower concentration of ethanol exposure, and decreased in higher concentration. Superoxide dismutase activity was also increased on ethanol exposure. But, ethanol feeding did not show any effect on glucose-6-phosphate dehydrogenase activity. Ethanol ingestion perturbs the antioxidant system in a dose and time dependent manner.     

Effects of chronic ethanol exposure on renal function tests and oxidative stress in kidney

After administration, ethanol and its metabolites go through the kidneys and are excreted into urine. The kidney seems to be the only vital organ generally spared in chronic alcoholics. Therefore, we investigated the multiple effects of chronic ethanol exposure on renal function tests and on oxidative stress related parameters in the kidney. Chronic ethanol (1.6 g ethanol/ kg body weight/ day) exposure did not show any significant change in relative weight (g/ 100g body weight) of kidneys, serum calcium level or glutathione s-transferase activity. However, urea and creatinine concentration in serum, and TBARS level in kidney elevated significantly, while reduced glutathione content and activities of glutathione peroxidase, glutathione reductase and superoxide dismutase diminished significantly after 12 weeks of ethanol exposure. Catalase activity showed increased activity after 4 weeks of ethanol exposure and decreased activity after 12 weeks of ethanol exposure. Genesis of renal ultrastructural abnormalities after 12 weeks of ethanol exposure may be important for the development of functional disturbances. This study revealed that chronic ethanol exposure for longer duration is associated with deleterious effects in the kidney.     

Effect of lecithin in the treatment of ethanol mediated free radical induced hepatotoxicity

Alcoholic liver disease (ALD) develops as a consequence of priming and sensitizing mechanisms rendered by cross-interactions of primary mechanistic factors and secondary risk factors. Liver damage due to consumption of alcohol may be caused by oxygen radicals such as superoxide and hydroxyl radicals, generated during the metabolism of ethanol by the microsomal oxidizing system. Lecithin, an important class of phospholipids contains choline, which is considered as lipotropic factor. The effects of this lecithin as a hepatoprotective drug on body weight and antioxidant status of ethanol-exposed rats were studied. The results were compared with the effects of tocopheryl acetate. From the present study, it can be concluded that ethanol-induced stress can be partly prevented by tocopheryl acetate, and showed best result. Abstination from alcohol also involved for little hepatic regeneration. Supplementation of lecithin showed better effect compared to abstination from alcohol on reversing the effect of ethanol induced liver damage in the present study. Moreover, preventive measures were found to be better than curative treatment. Antioxidants are likely to provide beneficial effects on hepatocyes via desensitization against oxidant stress while inhibiting primary mechanism for expression of proinflammatory and cytotoxic mediators. However, abstinence from alcohol, proper nutrition, and supplementation of antioxidants, vitamins and hepatoprotective drugs are some of the therapeutic options.     

Role of ethanol on aluminum induced biochemical changes on rat brain

Aluminum and alcohol, both are well-accepted neurotoxin. The plausible mechanisms for their neurotoxicity are also common. Therefore, the effect of ethanol on aluminum induced biochemical changes in rat brain is being studied. In the present study, ethanol exposure significantly affected the aluminum and protein content of brain. The activities of acid phosphatase and alkaline phosphatase were also changed. Aluminum exposure, on the other hand, contributed significantly in the alterations of aluminum content, acid phosphatase acivity and aspartate aminotransferase activity. Though ethanol co-exposure significantly influenced the aluminum load of brain, the interactions of these two neurotoxins were found to be significant only in case of acid phosphatase activity of brain. Therefore, it can be suggested that general neurotoxicity produced by aluminum is not modified by ethanol. However, the aluminum load caused by aluminum exposure, may be influenced by ethanol co-exposure.     

Oxidative stress is the primary event: Effects of ethanol consumption in brain

Damaging effects of reactive oxygen species on living systems are well documented. They include oxidative attack on vital cell constituents. Chronic ethanol administration is able to induce an oxidative stress in the central nervous system. In the present study, 16–18 week-old male albino rats of Wistar strain were exposed to different concentration of ethanol for 4 weeks. This exposure showed profound effect on body weight. Ascorbic acid level; and activities of alkaline phosphatase and aspartate transaminase in the brain are dependent on the concentration of ethanol exposure. Chronic ethanol ingestion elicits statistically significant increase in thiobarbituric acid reactive substances level and decrease in gluatathione level in the brain. It reduces superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities in a dose dependent manner. However, histological examination could not reveal any pathophysiological changes. Therefore, we conclude that biochemical alterations and oxidative stress related parameters respond early in alcoholism than the histopathological changes in brain.     

Cartap and carbofuran induced alterations in serum lipid profile of Wistar rats

Wistar rats of 6–8 weeks in age weighing between 120–150 g were exposed to the fixed doses of each of the carbamate pesticides such as cartap (50% LD₅₀) and carbofuran (50% LD₅₀) as well as a combination of these two with 25% LD₅₀ of each for one week. The effect of treatments was studied in terms of serum lipid parameters such as high-density lipoprotein, total cholesterol, triglyceride, low-density lipoprotein and very low-density lipoprotein. Treatment with individual doses of carbofuran (50% LD₅₀) and cartap (50 % LD₅₀) caused significant alterations in the levels of serum lipid parameters. The pesticides treatment resulted in marked decrease in the level of serum high-density lipoprotein where as that of other lipids got significantly elevated. Further, the rats exhibited relatively higher impact of pesticides when treated with the compounds in combination (25 % LD₅₀ of each). The results indicated that these compounds when used together may exert enhanced effect on the levels of serum lipids in rat.     

Effect of Lecithin and silymarin on D-galactosamine induced toxicity in isolated hepatocytes and rats

To investigate Lecithin for its hepatoprotective activity against D-galactosamine (D-GalN) induced toxicity in freshly isolated rat hepatocytes and animal models. Freshly isolated rat hepatocytes were exposed to Dgalactosamine (30 mM) along with/without lecithin (100 μg/ml) and the levels of selected liver enzymes were measured. Thirty six Wistar strain albino rats were used for the in vivo investigations. Lecithin 50 and 100 mg/kg.b.wt were administered for one week by oral route. Liver damage was induced by intra peritoneal administration of 400 mg/kg b.wt D-galactosamine. The antihepatotoxic effect of lecithin was observed in freshly isolated rat hepatocytes at concentration 100 μg/ml and was found to be similar to that of the standard silymarin used. Its in vivo hepatoprotective effect at 100 mg/kg b.wt was comparable with that of the standard silymarin at 100 mg/kg body weight. Lecithin was able to normalise the biochemical levels which were altered due to D-galactosamine intoxication in freshly isolated rat hepatocytes and also in animal models.     

Effect of nicorandil and amlodipine on bio-chemical parameters during isoproterenol induced myocardial necrosis in rats

Objective  To investigate the protective effect of nicorandil and amlodipine in isoproterenol induced myocardial necrosis in rats. Methods  The effect of nicorandil and amlodipine on bio-chemical parameters during isoproterenol induced myocardial necrosis in rats was examined by determining the activity of creatine phosphokinase (CK), lactate dehydrogenase (LDH), and transaminases (AST, ALT) in the serum of the animals. Results  Isoproterenol (150mg/kg/day) administered rats showed statistically significant rise in activities of LDH(1.02±0.19 to 1.85±0.05), CK(4.3±0.19 to 7.37±.27), AST(0.38±.03 to 0.78±.05) and ALT(0.19±.017 to 0.346±.027) in the serum. Pre-co-treatment of rats with nicorandil and amlodipine significantly lowered the raised levels of these enzymes and thereby restoring the enzyme activity to near normal as was clear from the chart i.e. LDH was 1.10±0.04, CK was 4.37±0.19, AST and ALT were 0.39±0.028 and 0.199±0.04 respectively. Conclusion  It is demonstrated that pre-co-treatment with nicorandil and amlodipine either alone or in combination help in providing protective effect on isoproterenol induced myocardial necrosis.     

瑶药四方藤提取物对类风湿关节炎模型大鼠抗风湿作用的研究

目的:研究四方藤60%乙醇提取物(EECH)对CII型胶原诱导类风湿关节炎模型(CIA)大鼠的抗风湿作用及其机制。方法:取40只Wistar大鼠随机分为正常对照组,模型组,阳性对照组,四方藤提取物高、低剂量组,每组8只。除正常对照组外,其余各组均采用CII胶原加氟氏完全佐剂法诱发类风湿性关节炎大鼠模型。EECH灌胃给予不同剂量提取物(2、0.5g.kg-1.d-1),模型组(雷公藤多苷片,1.5mg.kg-1.d-1),其余两组给予等量生理盐水,连续28天。测定大鼠血清炎症因子中TNF-α、IL-1β的表达,观察各组大鼠关节组织病理变化情况。结果:与模型组比较,EECH高、低剂量组可以显著降低CIA大鼠血清中炎症因子TNF-α、IL-1β的表达(P0.01)。病理检测表明,EECH可以显著改善CIA大鼠的关节病变。结论:EECH可对类风湿关节炎模型大鼠的关节具有明显的治疗作用,其机制可能与其下调血清中炎症因子中TNF-α、IL-1β的表达有关。     

Effect of type II collagen treatment on the antioxidant status in immune tissues of adjuvant induced arthritic rats

Adjuvant induced arthritis (AIA) is a model widely used to study Rheumatoid arthritis (RA). In the present study, lipid peroxides level in spleen and thymus of AIA rats was observed to be significantly high compared to normal rats. A significant decrease in ascorbic acid (ASA), reduced glutathione (GSH), superoxide dismutase activity (SOD) was also observed in spleen and thymus of AIA rats compared to normal rats. There was also a steady increase in the circulating immune complex level (CIC) throughout the experimental period in serum of AIA rats. In the present investigation, it was decided to study the effect of pre and post treatment with TYPE II collagen on the antioxidant status and the circulating immune complex level in AIA rats. The results from the present work indicates that the pretreatment with TYPE II collagen was effective in bringing significant changes on all the parameters studied in AIA rats. The post treatment with TYPE II collagen was effective in bringing significant changes on the CIC immune complex level and GSH content in the thymus tissue of AIA rats. The present work suggests that the pre treatment with TYPE II collagen was more effective in suppressing the disease than the post treatment.     

Effect of Hemodialysis on Plasma Myeloperoxidase Activity in End Stage Renal Disease Patients

End stage renal disease (ESRD) patients on hemodialysis (HD) have an increased oxidative stress, with a high risk of atherosclerosis and other co-morbid conditions. Recent studies have suggested that myeloperoxidase (MPO)—mediated oxidative stress may play a role in the pathogenesis of cardiovascular complications in dialysis patients. Furthermore, dialysis treatment ‘per se’ can aggravate oxidative stress. Hence this study was designed to determine whether HD leads to an alteration in the plasma levels of MPO and malondialdehyde (MDA), a marker of oxidative stress in ESRD patients on maintenance HD. To study the effect of HD, plasma MPO and MDA were determined before and after HD in forty ESRD patients (24 men and 16 women, age between 8 and 71 years, median being 40.5 years) on maintenance HD. Plasma MPO and MDA were assayed by spectrophotometric methods. Haematological and other biochemical parameters were obtained from patients’ case records. Plasma MPO and MDA levels were significantly higher after HD when compared with pre-dialysis levels (p < 0.05). There was no correlation between MPO and MDA (r = 0.184, p = 0.10) and other biochemical parameters (p > 0.05). However, there was a significant correlation between MPO and MDA with haemodialysis vintage (p < 0.05). In univariate regression analysis duration of HD (β = 1.470, p = 0.045, β = 0.388, p = 0.013), was independently associated with MPO and MDA. Although HD is indispensable for survival of patients with ESRD, it is fraught with undesirable side-effects, such as an increase in the plasma MPO and MDA levels. The elevated levels of MPO contribute to the increased oxidative stress as free radicals are produced by the reaction catalyzed by it.     

Effect of vitamin E supplementation on oxidative stress in hemodialysis patients

Hemodialysis represents a chronic stress status for its recipients. Many hypotheses state that this may be associated with oxidative stress. Thus, there may be deficiency of antioxidants like erythrocytic superoxide dismutase, catalase, vitamin E or increased generation of free radicals like superoxide anions. A study was carried out to investigate oxidant and antioxidant status in chronic renal failure patients undergoing hemodialysis and effect of vitamin E supplementation on these two status. Blood samples were collected from patients before and after hemodialysis and from controls. The samples were analyzed for quantitation of MDA as index of lipid peroxide, nitric oxide, vitamin E, vitamin C and enzymatic antioxidants namely erythrocyte SOD and catalase. As compared to controls, the levels of serum MDA were significantly increased and activities of erythrocyte SOD and catalase, levels of serum nitric oxide, serum vitamin E and plasma vitamin C were significantly decreased both before and after hemodialysis. The efficiency of vitamin E therapy in hemodialysis patients was assessed by re-evaluating oxidant and antioxidant status of same patients after supplementation of vitamin E. Vitamin E supplementation caused decrease in serum MDA and increase in levels of serum nitric oxide, vitamin E, vitamin C and activities of erythrocytic SOD and catalase. Our results suggest the presence of oxidative stress and the possible preventive role of vitamin E therapy in hemodialysis patients.     

Effect ofOcimum sanctum (Tulsi) and vitamin E on biochemical parameters and retinopathy in streptozotocin induced diabetic rats

This study was carried out to see the effect of the aqueous extract ofOcitum sanctum Linn (Tulsi) with Vitamin E on biochemical parameters and retinopathy in the streptozotocin-induced diabetic albino male rats. Adult albino male rats weighing 150–200 gm were made diabetic by intraperitoneal injection of streptozotocin in the dose 60 mg/kg in citrate buffer (pH 6.3). The diabetic animals were left for one month to develop retinopathy. Biochemical parameters like plasma glucose, oral glucose tolerance and glycosylated hemoglobin HbA_1c, were measured along with lipid profile, and enzymes like glutathione peroxidase (GPX), lipid peroxidase (LPO), superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) in normal, untreated diabetic rats and diabetic rats treated withOcimum sanctum L extracts and vitamin E. Fluorescein angiography test was done for assessing retinopathy. Results on biochemical parameters were analyzed statistically by using ANOVA followed by Dunnet's ‘t’-test. A p-value of <0.05 was considered as significant. Evaluation of biochemical profile in treated groups showed statistically significant reduction in plasma levels of glucose, HbA_1c, lipid profile and LPO, and elevation of GPX, SOD, CAT and GST. Treatment of the diabetic animals withOcimum sanctum and Vitamin E, alone and in combination for 16 weeks showed reversal of most of the parameters studied including plasma glucose levels. Angiography showed improvement in retinal changes following combined antidiabetic treatment.     

Effect of Isoproterenol on Tissue Defense Enzymes,Hemodynamic and Left Ventricular Contractile Function in Rats

Present study investigated the effects of isoproterenol-induced oxidative stress on hemodynamic and ventricular functions in rats. Subcutaneous injections of isoproterenol (85 mg/kg for two consecutive days at 24 h interval) significantly decreased myocardial antioxidant enzymes; superoxide dismutase, catalase and glutathione peroxidase in heart. Isoproterenol-induced oxidative stress was also evidenced by significant depletion of reduced glutathione and increased formation of lipid peroxidation product, thiobarbituric acid reactive substances along with depletion of myocyte injury specific marker enzymes; creatine phosphokinase isoenzyme and lactate dehydrogenase. The deleterious outcome of oxidative stress on hemodyanmic parameters and ventricular function were further evidenced by decreased systolic, diastolic and mean arterial blood pressure, heart rate, ventricular contractility; [(+)LVdP/dt] and relaxation; [(−)LVdP/dt], along with an increased left ventricular end diastolic pressure (LVEDP). Subsequent to changes in heart rate and arterial pressure, isoproterenol also decreased rate pressure product. Present study findings clearly demonstrate the detrimental outcome of isoproterenol induced-oxidative stress on cardiac function and tissue antioxidant defense and substantiate its suitability as an animal model for the evaluation of cardioprotective agents.     

Effect of folic acid and vitamin B<Subscript>12</Subscript> administration on phenytoin induced toxicity in rats

Folic acid and vitamin B₁₂ are very important vitamins needed for normal cellular metabolic activities. The effects of folic acid and vitamin B₁₂ on liver integrity of growing Wistar albino rats following therapeutic dose of phenytoin administration were investigated. The activities of serum AST, ALT, ALP were investigated. Serum total protein level and lipid profile were also measured as indices of biochemical changes. The ingestion of phenytoin alone in rats significantly reduced serum protein while AST, ALT activities incresed as compared to the control (P<0.05). Supplementation of phenytoin with oral administration of 70microgram/kg body wt of folic acid resulted in a significant reversal in serum total protein and suppression in serum AST and ALT activities. Vitamin B₁₂ supplementation did not afford any significant protection against the effect of phenytoin ingestion but rather phenytoin toxicity was exacerbated in this study. However, the combined effects of vitamin B₁₂ and folic acid ameliorated the effects of phenytoin on serum enzymes of experimental rats. The effect of combination of phenytoin with folic acid or folic acid and vitamin B₁₂ is an interesting finding. Supplementation of phenytoin with folic acid or combination of these vitamins may be recommended for the purpose of ameliorating the adverse biochemical changes which are associated with phenytoin therapy. Further work is ongoing to help elucidate the effects of phenytoin and these vitamins on oxidative stress inducing mechanism.     

Antioxidant effect ofPhyllanthus emblica fruits on healing of indomethacin induced gastric ulcer in rats

Post-treatment of the indomethacin induced ulcerated rats at the optimal dose of 100 mg/kg body-wt. orally for 7 consecutive days with the lyophilized aqueous extract of the fruits ofPhyllanthus emblica L. syn.Emblica officinalis Gaertn. (Euphorbiaceae) exhibited highly significant (p<0.001) enhancement of secretion of catalase, reduced glutathione and decrease in malonyldialdehyde (MDA). Furthermore, the gross morphological observation and highly significant (p<0.001) decrease of ulcer index (81.43%) indicated healing effect of the extract on gastric ulcer.     

Hepatoprotective effect of<Emphasis Type="Italic">Hygrophila spinosa</Emphasis> and<Emphasis Type="Italic">Cassia occidentalis</Emphasis> on carbon tetrachloride induced liver damage in experimental rats

The present study was undertaken to analyze the levels of some known antioxidant (both enzymic and non enzymic) activities in the rootsof Hygrophila spinosa andCassia occidentalis also to find out the hepatoprotective effect of the same in carbon tetrachloride induced liver damage in albino rats. The roots were found to be rich in antioxidants. Liver damage in rats were induced by carbon tetrachloride. To find out the hepatoprotective activity, the aqueous extract of the plant root samples were administrated to rats for 15 days. The serum marker enzymes Aspartate transaminase, Alanine transaminase and Gama Glutamyl were measured in experimental animals. The increased enzyme levels after liver damage with carbon tetrachloride were nearing to normal value when treated with aqueous extract of the root samples. Histopathological observation also proved the hepatoprotectivity of the root samples.     

Preliminary studies on the hypoglycemic effect of <Emphasis Type="Italic">Peganum harmala</Emphasis> L. Seeds ethanol extract on normal and streptozotocin induced diabetic rats

Peganum harmala L. (Zygophyllaceae) is a traditional medicine used for the treatment of variety of human ailments, including antidepression, hallucination, antileishmaniasis etc. We report for first time the hypoglycemic activity of the ethanolic extract of this plant at two dose levels of 150 and 250mg/kg bw in sucrose challenged normal as well as in rats with streptozotocin induced diabetes. The oral administration of ethanolic extract causes maximum fall of blood glucose level to 22.9% (p<0.05) and 29.4% (p<0.01) respectively with the two doses in normal and 30.3% (p<0.01) and 48.4% (p<0.001) in diabetic rats. The standard drug metformin treated group showed 28.0% (p<0.01) and 45.5% (p<0.001) respectively in normal and diabetic rats. The above results show that the ethanolic extract of P. harmala is as effective as metformin in reducing the blood glucose levels of normoglycemic and streptozotocin-induced diabetic rats.