Protective effect of ferulic acid on nicotine-induced DNA damage and cellular changes in cultured rat peripheral blood lymphocytes: a comparison with N-acetylcysteine.

Nicotine is the major pharmacologically active substance in cigarette smoke and plays an important etiological role in the development of lung cancer. Incidence of cancer may be related to oxidative damage to host genome by nicotine. These oxidative actions may be modified by the phytochemicals present in food. The present study describes the protective effect of ferulic acid (FA), a naturally occurring nutritional compound on nicotine-induced DNA damage and cellular changes in cultured rat peripheral blood lymphocytes in comparison with N-acetylcysteine (NAC), a well-known antioxidant. One-hour exposure of lymphocytes to nicotine at the doses of 0.125, 0.25, 0.5, 1, 2, 3 and 4 mM induced a statistically significant dose-dependent increase in the levels of thiobarbituric acid reactive substances (TBARS), a lipid peroxidative marker and decrease in the levels of reduced glutathione (GSH), an important endogenous antioxidant. The lowest concentration eliciting significant damage was 1 mM nicotine and maximum damage was observed with 3 mM concentration. Hence, the test concentration was fixed at 3 mM nicotine. We have used 5 different doses of FA (10, 50, 100, 150 and 300 microM) and NAC (0.25, 0.5, 1, 2 and 4 mM) to test their protective effects. In all the groups, FA and NAC showed a dose-dependent inhibitory effect. Maximum protection was observed at the dose of 150 microM FA and 1mM NAC. So, 150 microM FA and 1mM NAC were used for further studies. There was a significant increase in the levels of lipid peroxidative index (TBARS and hydroperoxides (HP)), severity of DNA damage (evaluated by comet assay) in nicotine-treated group, which were significantly decreased in FA and NAC-treated groups. Nicotine treatment significantly decreased the endogenous antioxidant status viz., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), GSH, vitamin A, E and C. Co-administration of FA and NAC to nicotine-treated lymphocytes showed a significant increase in the antioxidant status. The protective effect of FA was merely equal to that of NAC effect. FA and NAC treatment alone did not produce any toxicity to the normal lymphocytes at their effective doses. On the whole, there is overwhelming evidence that FA has the ability to modulate DNA damage and a variety of cellular changes that occur during nicotine-induced toxicity in rat peripheral blood lymphocytes.

Curcumin ameliorates oxidative stress during nicotine-induced lung toxicity in Wistar rats.

Nicotine, a major toxic component of cigarette smoke has been identified as a major risk factor for lung related diseases. In the present study, we evaluated the protective effects of curcumin on lipid peroxidation and antioxidants status in bronchoalveolar lavage fluid (BALF) and bronchoalveolar lavage (BAL) of nicotine treated Wistar rats. Lung toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5 mg/kg body weight (5 days a week, for 22 weeks) and curcumin (80 mg/kg body weight) was given simultaneously by intragastric intubation for 22 weeks. Measurement of biochemical marker enzymes: alkaline phosphatase, lactate dehydrogenase, lipid peroxidation and antioxidants were used to monitor the antiperoxidative effects of curcumin. The increased biochemical marker enzymes as well as lipid peroxides in BALF and BAL of nicotine treated rats was accompanied by a significant decrease in the levels of glutathione, glutathione peroxidase, superoxide dismutase and catalase. Administration of curcumin significantly lowered the biochemical marker enzymes, lipid peroxidation and enhanced the antioxidant status. The results of the present study suggest that curcumin exert its protective effect against nicotine-induced lung toxicity by modulating the biochemical marker enzymes, lipid peroxidation and augmenting antioxidant defense system.

Toxic effects of sunflower oil on ethanol treated rats.

In the present study, we investigated the effect of raw as well as thermally oxidized sunflower oil (commercially available) on ethanol induced hepatotoxicity. Ethanol was given to animals at a level of 20% and sunflower oil at a level of 15%. Results show higher activity of plasma aspartate transaminase (AST) and alkaline phosphatase (ALP) and also higher levels of plasma and tissue cholesterol, phospholipids and triglycerides both in alcohol+raw as well as thermally oxidized oil groups. The level of cholesterol and triglycerides increased significantly in the liver of rats given alcohol alone, alcohol and raw as well as thermally oxidized oil but the level of phospholipids decreased. The activity of phospholipase A and phospholipase C in liver was found to be increased significantly in alcohol alone, alcohol+oil groups as compared to control group. Histopathological changes in the liver of alcohol and alcohol+oil groups were in good correlation with biochemical parameters. The liver samples of alcohol administered rats showed both microvesicular and macrovescicular type of fatty changes, where as alcohol+oil fed groups showed inflammatory cell infiltrate in the portal triad, microvesicular and macrovesicular type of fatty changes and feathery degeneration of hepatocytes. Studies on the phospholipid fatty acid composition in the liver showed the presence of a number of fatty acids in the alcohol and oil treated groups, which are not present in the control group. The results obtained thus indicate hepatotoxic and hyperlipidaemic effects of alcohol and oil given together.