Protective effects of gallic acid on hepatic lipid peroxide metabolism, glycoprotein components and lipids in streptozotocin-induced type II diabetic Wistar rats.

We evaluated the protective effects of gallic acid (3,4,5-trihydroxybenzoic acid) on hepatic lipid peroxidation products, antioxidants, glycoprotein components, and lipids in streptozotocin-induced type II diabetic rats. To induce type II diabetes, rats were injected with streptozotocin intraperitoneally at a single dose of 40 mg/kg. Gallic acid (10 and 20 mg/kg) treatment was given to diabetic rats orally using an intragastric tube daily for 21 days. Streptozotocin-induced diabetic rats showed a significant increase in the levels of blood glucose, hepatic lipid peroxidation products, glycoprotein components, lipids, and the activity of HMG-CoA reductase and a significant decrease in the levels of plasma insulin and liver glycogen. In addition to this, the activities/levels of hepatic antioxidants were decreased in diabetic rats. Gallic acid (10 and 20 mg/kg) treatment showed significant protective effects on all the biochemical parameters studied in diabetic rats. Thus, our study shows the antihyperglycemic, antilipid peroxidative, antioxidant, and antilipidemic effects of gallic acid in streptozotocin-induced type II diabetic rats. A diet containing gallic acid may be beneficial to type II diabetic patients.

The cardioprotective effects of a combination of quercetin and α-tocopherol on isoproterenol-induced myocardial infarcted rats.

The present study aims to evaluate the combined protective effects of quercetin and α-tocopherol on isoproterenol-treated myocardial infarcted rats. Male albino Wistar rats were pretreated with a combination of quercetin (10 mg/kg) and α-tocopherol (10 mg/kg) daily for 14 days. After the pretreatment, rats were injected isoproterenol (100 mg/kg) to induce myocardial infarction. Isoproterenol-treated rats showed increased levels of serum troponins and increased intensities of serum lactate dehydrogenase-1 and -2 isoenzyme bands. Isoproterenol treatment also showed significant decreased levels of antioxidant system and significant increased levels of plasma lipid peroxidation, plasma uric acid, and the heart calcium. Furthermore, isoproterenol-treated rat's electrocardiogram showed elevated ST segments. Combined pretreatment with quercetin and α-tocopherol normalized all the biochemical parameters and minimized the alterations in electrocardiogram. Histopathology of myocardium also confirmed the cardioprotective effects of quercetin and α-tocopherol. In vitro studies confirmed the mechanism of action of quercetin and α-tocopherol. Thus, quercetin and α-tocopherol exhibited cardioprotective effects against isoproterenol-induced cardiotoxicity due to their scavenging free radicals, improving antioxidants and maintaining Ca(2+) levels. Our study also showed that combined pretreatment (quercetin and α-tocopherol) was highly effective than single pretreatment (quercetin or α-tocopherol).

Protective effects of combination of quercetin and α-tocopherol on mitochondrial dysfunction and myocardial infarct size in isoproterenol-treated myocardial infarcted rats: biochemical, transmission electron microscopic, and macroscopic enzyme mapping evidences.

Mitochondrial dysfunction plays an important role in the pathology of myocardial infarction. We evaluated the combined protective effects of quercetin and α-tocopherol on mitochondrial damage and myocardial infarct size in isoproterenol-induced myocardia- infarcted rats. Rats were pretreated with quercetin (10 mg/kg) alone, α-tocopherol (10 mg/kg) alone, and combination of quercetin (10 mg/kg) and α-tocopherol (10 mg/kg) orally using an intragastric tube daily for 14 days. After pretreatment, rats were induced myocardial infarction by isoproterenol (100 mg/kg) at an interval of 24 h for 2 days. Isoproterenol treatment caused significant increase in mitochondrial lipid peroxides with significant decrease in mitochondrial antioxidants. Significant decrease in the activities of isocitrate, succinate, malate, and α-ketoglutarate and NADH dehydrogenases and cytochrome-c-oxidase, significant increase in calcium, and significant decrease in adenosine triphosphate were observed in mitochondria of myocardial infarcted rats. Combined pretreatment with quercetin and α-tocopherol normalized all the biochemical parameters and preserved the integrity of heart tissue and restored normal mitochondrial function in myocardial-infarcted rats. Transmission electron microscopic findings on heart mitochondria and macroscopic enzyme mapping assay on the size of myocardial infarct also correlated with these biochemical parameters. The present study showed that combined pretreatment was highly effective than single pretreatment.

Protective effects of rutin on mitochondrial damage in isoproterenol-induced cardiotoxic rats: an in vivo and in vitro study.

Consumption of diets rich in flavonoids is associated with reduced risk of cardiovascular diseases such as myocardial infarction. Cardiotoxicity was induced in rats by subcutaneous injection of isoproterenol at an interval of 24 h for 2 days. Isoproterenol-induced rats showed a significant increase in the levels of heart mitochondrial lipids, lipid peroxidation products, calcium and a significant decrease in the activities/levels of mitochondrial antioxidants, enzymes and adenosine triphosphate. Isoproterenol-induced rats also showed an increase in the intensities of serum lactate dehydrogenase-1 and 2 isoenzyme bands. Pretreatment with rutin at the dose of 80 mg/kg daily for 42 days to isoproterenol-induced rats prevented all the biochemical alterations. Transmission electron microscopic study also confirmed the protective effects of rutin on the structure of heart mitochondria. Thus, rutin reduced the extent of mitochondrial damage induced by isoproterenol and prevented cardiac mitochondrial dysfunction. The possible mechanisms for the observed effects of rutin could be due to scavenging free radicals, lowering lipid peroxides, lipids and calcium, improving multienzyme activities, glutathione levels, adenosine triphosphate levels, thereby improving cardiac mitochondrial structure and function. This study may have a significant impact on myocardial infarcted patients.

Pretreatment with a combination of quercetin and alpha-tocopherol ameliorates adenosine triphosphatases and lysosomal enzymes in myocardial infarcted rats.

AIMS: Membrane bound adenosine triphosphatases (ATPases) and lysosomal enzymes play an important role in the pathology of myocardial infarction. This study was aimed to evaluate the combined preventive effects of quercetin and alpha-tocopherol on membrane bound ATPases and lysosomal enzymes in isoproterenol induced myocardial infarcted rats. MAIN METHODS: Male Wistar rats were pretreated with a combination of quercetin (10mg/kg) and alpha-tocopherol (10mg/kg) daily for 14 days. After the pretreatment period, isoproterenol (100mg/kg) was injected to rats at an interval of 24h for two days to induce myocardial infarction. The activities of ATPases and lysosomal enzymes were assayed. KEY FINDINGS: Isoproterenol treated rats showed decreased levels of heart creatine kinase and lactate dehydrogenase. The activity of sodium potassium adenosine triphosphatase was decreased and the activities of magnesium adenosine triphosphatase and calcium adenosine triphosphatase were increased in isoproterenol treated rats. Also, the activities of beta-glucuronidase, beta-N-acetylglucosaminidase, beta-galactosidase, cathepsin-B and D were increased (serum and heart), but the activities of beta-glucuronidase and cathepsin-D were decreased in lysosomal fraction and increased in cytosolic fraction of the heart in isoproterenol treated rats. Furthermore, the heart lipid peroxidation products were increased in isoproterenol treated rats. Combined pretreatment with quercetin and alpha-tocopherol to isoproterenol treated rats normalized all the biochemical parameters studied. The observed effects are due to their membrane stabilizing property and this property might be due to decreased lipid peroxidation. SIGNIFICANCE: Our study demonstrated that combined pretreatment was better than single pretreatment. This study may have significant impact on myocardial infarcted patients.

Combined effects of quercetin and alpha-tocopherol on lipids and glycoprotein components in isoproterenol induced myocardial infarcted Wistar rats.

This study was aimed to evaluate the combined effects of quercetin and alpha-tocopherol on lipid metabolism and glycoprotein components in isoproterenol induced myocardial infarction in Wistar rats. Myocardial infarction in rats was induced by isoproterenol (100mg/kg) at an interval of 24h for 2 days. Quercetin (10 mg/kg) and alpha-tocopherol (10 mg/kg) were given to rats as pretreatment for 14 days orally using an intragastric tube. Quercetin and alpha-tocopherol significantly reduced the levels of cholesterol, triglycerides and free fatty acids in the serum and heart and serum phospholipids and significantly increased the levels of heart phospholipids in isoproterenol induced rats. They also significantly decreased the activity of plasma and liver 3-hydroxy-3-methylglutaryl-coenzyme-A reductase and increased the activity of plasma and liver lecithin cholesterol acyl transferase in isoproterenol treated rats. In addition to this, they also significantly reduced the levels of hexose, hexosamine, fucose and sialic acid in the serum and heart of isoproterenol treated rats. Quercetin and alpha-tocopherol also showed significant decrease in plasma lipid peroxidation products (thiobarbituric acid reactive substances and lipid hydroperoxides). Pretreatment with quercetin alone and alpha-tocopherol alone showed significant effect in all the biochemical parameters in myocardial infarcted rats. But, combined pretreatment with quercetin and alpha-tocopherol normalized all the above mentioned biochemical parameters in isoproterenol treated myocardial infarction in rats. Thus, the experiment clearly showed that quercetin and alpha-tocopherol prevented the accumulation of lipids and glycoprotein components in myocardial infarcted rats by their anti-lipid peroxidative effect. This study also showed that combined pretreatment was better than single pretreatment.

Combined treatment with naringin and vitamin C ameliorates streptozotocin-induced diabetes in male Wistar rats.

Diet and nutrition have substantial impact on reducing the incidence of diabetes mellitus, where oxidative stress is an important etiopathological factor. The combined protective role of low dose of naringin (15 mg kg(-1)) and vitamin C (25 mg kg(-1)) and high dose of naringin (30 mg kg(-1)) and vitamin C (50 mg kg(-1)) on streptozotocin (STZ)-induced toxicity was studied in male Wistar rats. To induce type II diabetes mellitus, rats were injected with STZ intraperitoneally at a dose of 45 mg kg(-1) body weight. STZ-induced diabetic rats showed significant increase in blood glucose, water intake, food intake and glycated hemoglobin and significant decrease in plasma insulin, total hemoglobin, body weight and liver glycogen. Diabetic rats also showed significant decrease in the activity of hexokinase and significant increase in the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase in liver and kidney. The levels of plasma thiobarbituric acid reactive substances, lipid hydroperoxides and vitamin E were elevated while the level of reduced glutathione was decreased in diabetic rats. Glycoprotein components such as hexose, hexosamine, fucose and sialic acid were increased in plasma, liver and kidney of diabetic rats. Oral administration of high doses of naringin (30 mg kg(-1)) and vitamin C (50 mg kg(-1)) to diabetic rats for a period of 21 days normalized all the above-mentioned biochemical parameters. The effect exerted by naringin (30 mg kg(-1)) and vitamin C (50 mg kg(-1)) was similar to the effect exerted by insulin (6 units kg(-1)). Thus, our study shows the antihyperglycemic and antioxidant effects of naringin and vitamin C in STZ-induced type II diabetes mellitus in rats.