Cardioprotective response to chronic administration of vitamin E in isoproterenol induced myocardial necrosis: Hemodynamic,biochemical and ultrastructural studies

The present study evaluated the cardioprotective potential of vitamin-E by studying its effect on hemodynamic parameters, lipid peroxidation, myocyte injury marker and ultrastructural changes in model of isoproterenol-induced myocardial necrosis in rats. Wistar albino male rats (150–200 g) were randomly divided into saline, ISP control, and vit E groups. Vitamin E group was administered vitamin E at a dose of 100mg/kg/day while saline and ISP control groups received saline orally for one month. On 29^th and 30^th day, ISP (85 mg/kg, sc) was administered at an interval of 24 h to vit E and ISP control rats. On 31^st day, rats of all groups were anesthetized and hemodynamic parameters were recorded. At the end of experimentation, animals were sacrificed; hearts were excised and processed for biochemical and ultrastructural studies. ISP administration produced marked cardiac necrosis as evidenced by significant decrease in my ocardial creatine kinase-MB as well as increase in malonaldialdehyde levels. ISP-induced myocardial necrosis resulted in myocardial dysfunction as evidenced by significant depression in heart rate and mean arterial pressure in the ISP control group as compared to saline control. Salient ultrastructural changes including extensive loss of myofibrils, muscle necrosis, loss of mitochondria, and formation of several intracytoplasmic vacuoles and lipid droplets further confirmed the ISP-induced myocardial damage. However, subsequent to ISP challenge, vit E treatment significantly preserved the myocardium by restoring myocardial CK-MB activity, inhibiting the ISP-induced lipid peroxidation and ultrastructural changes. Additionally, pre-and co-treatment of vit E prevented the deleterious ultrastructural changes caused by ISP. These beneficial effects of chronic vit E treatment also translated into significant restoration of the altered hemodynamic parameters. The present study clearly demonstrated the cardioprotective potential of vit E at dose of 100 mg/kg in ISP-induced model of myocardial necrosis in rats. The significant restoration of altered hemodynamic parameters, myocardial CK-MB activity, prevention of ISP-induced rise in lipid peroxidation and ultrastructural changes may confirm its cardioprotective effect.     

Cardioprotective activity of synthetic guggulsterone (E and Z-isomers) in isoproterenol induced myocardial ischemia in rats: A comparative study

Guggulsterone, a mixture of cis (E) and trans (Z) isomers (7∶3 w/w) was synthesized from 16-DPA. The isomers were separated by column chromatography and evaluated for cardioprotective and antioxidant activities. Myocardial necrosis induced by isoproterenol in rats caused marked increase in serum creatine phosphokinase and glutamate pyruvate transaminase. Simultaneously in ischemic heart, phospholipase, xanthine oxidase and lipid peroxides were enhanced following depletion of glycogen, phospholipids and cholesterol. Treatment with guggulsterone and its both isomers at the dose of 50 mg/kg po., significantly protected cardiac damage as assessed by the reversal of blood and heart biochemical parameters in ischemic rats. The cardioprotective activity of guggulsterone and of both the isomers were compared with that of gemfibrozil at the same doses. Guggulsterone and both the isomers at tested concentrations (5–20mM) inhibited oxidative degradation of lipids in human low-density lipoprotein and rat liver microsomes induced by metal ionsin vitro. The drug counteracted against the generation of superoxide anions (O₂) and hydroxyl radicals (OH⁻) in non-enzymic test systems. It is suggested that cardioprotective and antioxidant activities of synthetic guggulsterone and guggulsterone obtained from gum resinCommiphora mukul that contains isomers E & Z in the ratio of 46∶54w/w are the same.     

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 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 exogenous L-ornithine L-aspartate on ethanol induced testicular injury in Wistar rats

To investigate reversibility of ethanol induced testicular injuries on treatment with L-ornithine-L-aspartate, male Wistar rats were treated with ethanol (1.6g/kg b.wt/day) and L-ornithine- L-aspartate (200mg/kg b.wt/ day) for 4 weeks. L-ornithine-L-aspartate effectively prevented the ethanol induced body and testes weight reduction; changes in testicular weight well correlated with body weight. Drug exhibited an ability to counteract ethanol induced oxidative challenge as it effectively reduced testicular TBARS and increased tissue ascorbic acid, GSH and activities of superoxide dismutase, catalase, GSH-Red and Se-GSH-Px. However the drug didn’t show promising effect on inhibitory effect of ethanol on testicular D5, 3-beta and 17-beta HSD (hydroxy steroid dehydrogenase).     

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.     

Biochemical activity of selenium and glutathione on country made liquor (CML) induced hepatic damage in rats

The serum and hepatic enzymes of rats were studied after exposed to country made liquor (CML) along with two chelating agents (glutathione and Selenium). There was a significant increase in several serum enzyme levels (viz., aspartate transaminase, alanine transaminase, alkaline phosphatase, sorbitol dehydrogenase, glutamate dehydrogenase, bilirubin) and decrease in various hepatic enzymes (Succinic dehydrogenase, Glucose 6-phosphatase, 5'Nucleotiease, Acid phosphatase, Acid ribonuclease, Cytochrome P-450) due to repeated administration of CML (2ml/100g of body weight). Results of this study revealed that the GSH and Se could give a significant protective action in serum and hepatic enzymes of CML exposed rats.     

Effect of vitamin E on the platelet xanthine oxidase and lipid peroxidation in the patients of myocardial infarction

Platelets play important role in precipitating ischaemic myocardial syndromes in many ways. One of the consequences of ischaemic diseases is excessive generation of oxygen derived free radicals that have numerous pathophysiological consequences. Platelet pro-oxidant enzyme, xanthine oxidase is one of the sources of generation of free radicals. In the present paper, we report the effect of administration of vitamin E along with aspirin on the levels of platelet xanthine oxidase and extent of free radical mediated damage in the patients reperfused after myocardial infarction. Our findings show that administration of 400 mg. vitamin E for six days along with 80 mg. aspirin has an excellent anti-oxidant effect as evidenced by reduced platelet xanthine oxidase activity and lowering of malondialdehdye (MDA) levels which is an index of the extent of free radical mediated damage.     

Hypoglycaemic, hypolipidemic and antioxidant properties of tulsi (Ocimum sanctum linn) on streptozotocin induced diabetes in rats

Effect of oral administration of 200 mg/Kg body weight of the aqueous extract ofOcimum sanctum (Tulsi) mixed with diet for eight weeks to diabetic (streptozotocin induced) rats was studied. There was significant reduction in fasting blood glucose, serum lipid profile, lipid peroxidation products, (LPO) and improvement in glucose tolerance. The aqueous extract also decreased LPO formation (thiobarbituric acid reactive substances TBARS) and increased antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione transferase (GT) and one antioxidant reduced glutathione (GSH) in plasma and rat liver, lung, kidney and brain. The decrease in TBARS and increase in GSH, SOD, CAT, GPX, and GT clearly shows the antioxidant property ofOcimum sanctum.     

Effect ofCrataeva nurvala bark decoction on enzymatic changes in liver of normal and stone forming rats

The influence of Crataeva nurvala bark decoction was studied in calcium oxalate stone forming rats, in relation to oxalate metabolism in liver. The activities of the major oxalate synthesizing enzymes in liver namely, glycollate oxidase (GAO) and lactate dehydrogenase (LDH) were significantly increased in the calculogenic group. Bark decoction treatment lowered the liver GAO activity considerably. Transport ATPases (Na⁺, K⁺ and Ca²⁺-ATPases) and alkaline phosphatase were enhanced in rats fed calculi producing diet, while the activities of acid phosphatase, inorganic pyrophosphatase and aminotransferases were slightly reduced. Bark decoction administration produced a marginal decrease in Na⁺, K⁺-ATPase and increase in aspartate aminotransferase activities, without significantly altering other enzyme activities. The decrease in liver GAO activity seen during bark decoction treatment, with concomitant decrease in kidney oxalate level, may prove beneficial as a prophylactic measure in preventing stone recurrence.     

Altered maternal thyroid function: Effect of L-carnitine supplementation on fetal and neonatal myocardial free fatty acid oxidation,in vitro

Effect of L-carnitine supplementation on myocardial free fatty acid oxidation,in vitro, in offsprings born of hypothyroid and hyperthyroid mothers was studied in rats. L-carnitine supplementation stimulated myocardial fatty acid oxidation during gestational period in offspring born of control and hyperthyroid mothers. In contrast L-carnitine supplementation induced stimulation in myocardial fatty acid oxidation was very less in fetuses born of hypothyroid mothers. However, in neonates born of hypothyroid mothers L-carnitine stimulated myocardial fatty acid oxidation to a great extent. The results suggested that during maternal hypothyroidism low availability of thyroid hormones to fetuses through maternal circulation and availability of less carnitine to neonates due to hypolactation might be responsible for decreased myocardial free fatty acid utilization. In neonates born of hypothyroid mothers and with cardiac energy insufficiency parenteral carnitine supplementation might be of great help to prevent mortality and morbidity of such offsprings.     

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。