Expression pattern of matrix metalloproteinases in alcohol- and thermally oxidized sunflower oil-induced toxicity: protective role of an aminothiazole derivative.

The matrix metalloproteinases (MMPs) are a family of secreted and membrane-bound zinc endopeptidases. Collectively, these enzymes can degrade all of the components of the extracellular matrix including collagen, fibronectin, laminin, and basement membrane glycoproteins. Regulation in expression and activation of proteinases is one of the most important mechanisms in organ morphogenesis. Fibrosis is a dynamic pathological process with a net accumulation of extracellular matrix proteins. In the present communication, we have investigated the changes that occur in the activity of liver MMPs in normal and in pathological conditions. The activity of MMPs was increased in thermally oxidized sunflower oiland alcohol-treated groups, whereas the activity was decreased in the thermally oxidized oil + alcohol-fed group when compared with the normal control group. The activity was positively modulated when dendrodoine analogue [4-amino-5-benzoyl- 2(4-methoxyphenylamino)thiazole] was administered along with ethanol and thermally oxidized oil, which indicates the protective effect of this drug.

Comparative effects of curcumin and its analog on alcohol- and polyunsaturated fatty acid-induced alterations in circulatory lipid profiles.

Excessive alcohol intake induces hyperlipidemia. Studies suggest that natural principles and their analogs are known to possess anti-hyperlipidemic properties. In the present work we tested the effect of curcumin, an active principle of turmeric (Curcuma longa), and a curcumin analog on alcohol- and thermally oxidized polyunsaturated fatty acid (deltaPUFA)- induced hyperlipidemia. Male albino Wistar rats were used for the experimental study. Anti-hyperlipidemic activity of curcumin and curcumin analog was evaluated by analyzing the levels of cholesterol, triglycerides (TGs), phospholipids (PLs), and free fatty acids (FFAs). The results showed that the levels of cholesterol, TGs, PLs, and FFAs were increased significantly in alcohol-, deltaPUFA-, and alcohol + deltaPUFA-treated groups, which were brought down significantly on treatment with either of the curcuminoids. Curcumin analog treatment was found to be more effective than curcumin treatment. From the results obtained, we conclude that both curcumin and its analog effectively protect the system against alcohol- and deltaPUFA-induced hyperlipidemia and are possible candidates for the treatment of hyperlipidemia.

Comparative effects of curcumin and an analog of curcumin on alcohol and PUFA induced oxidative stress.

PURPOSE: Alcoholic liver disease is a major medical complication of alcohol abuse and a common liver disease in western countries. Increasing evidence demonstrates that oxidative stress plays an important etiologic role in the development of alcoholic liver disease. Alcohol alone or in combination with high fat is known to cause oxidative injury. The present study therefore aims at evaluating the protective role of curcumin, an active principle of turmeric and a synthetic analog of curcumin (CA) on alcohol and thermally oxidised sunflower oil (DeltaPUFA) induced oxidative stress. METHODS: Male albino Wistar rats were used for the experimental study. The liver marker enzymes: gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), the lipid peroxidative indices: thiobarbituric acid reactive substances (TBARS) and hydroperoxides (HP) and antioxidants such as vitamin C, vitamin E, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) were used as biomarkers for testing the antioxidant potential of the drugs. RESULTS: The liver marker enzymes and lipid peroxidative indices were increased significantly in alcohol, DeltaPUFA and alcohol + DeltaPUFA groups. Administration of curcumin and CA abrograted this effect. The antioxidant status which was decreased in alcohol, DeltaPUFA and alcohol + DeltaPUFA groups was effectively modulated by both curcumin and CA treatment. However, the reduction in oxidative stress was more pronounced in CA treatment groups compared to curcumin. CONCLUSION: In conclusion, these observations show that CA exerts its protective effect by decreasing the lipid peroxidation and improving antioxidant status, thus proving itself as an effective antioxidant.

Alcohol and thermally oxidized pufa induced oxidative stress: role of N-acetyl cysteine.

Alcohol related disabilities are one of the world's major public health concerns. The effects of alcohol intake include alteration of redox state, acetaldehyde and free radical production, which lead to membrane damage. The damage caused by alcohol is enhanced by polyunsaturated fatty acid ingestion. When alcohol is taken along with thermally oxidized sunflower oil, the toxicity is still more pronounced due to toxic metabolites produced during heating. In our study, we have analysed the effects of a thiol supplier N-acetyl cysteine on alcohol, thermally oxidized sunflower oil and alcohol + thermally oxidized sunflower oil induced toxic effects in male Wistar rats. The activities of liver marker enzymes (alkaline phosphatase and gamma-glutamyl transferase), triglycerides in plasma and lipid peroxidative indices (thiobarbituric acid reactive substances and hydroperoxides) were increased in these groups when compared to normal, which were brought down in N-acetyl cysteine treated groups. The antioxidant status (Superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase) was decreased in tissues of these groups, which were found to be improved in N-acetyl cysteine treated groups. Thus our results show that N-acetyl cysteine regresses the oxidative damage induced by Alcohol, thermally oxidized sunflower oil and alcohol + thermally oxidized sunflower oil.

Hepatoprotective role of ferulic acid: a dose-dependent study.

Alcohol use is contributing to an unprecedented decline in life expectancy. Damage to the liver after ethanol administration is a well-known phenomenon. Free radical mechanisms have been proposed to play a part in ethanol-induced liver toxicity. Ingestion of diets rich in polyunsaturated fatty acids (PUFAs) along with alcohol is known to result in enhanced liver damage. The present work is aimed at evaluating the protective role of ferulic acid, a naturally occurring plant component, on alcohol- and PUFA-induced liver toxicity. Three different doses of ferulic acid (10, 20, and 40 mg/kg of body weight) were administered to rats given alcohol, heated PUFA (DeltaPUFA), and alcohol + DeltaPUFA. Influence of ferulic acid on alcohol-and PUFA-induced liver damage was evaluated by analyzing the activities of the liver marker enzymes alkaline phosphatase, gamma-glutamyl transferase, alanine transaminase, and aspartate transaminase. The activities of these liver marker enzymes were increased in the alcohol, DeltaPUFA, and alcohol + DeltaPUFA groups but were decreased significantly on treatment with ferulic acid. The low dose (10 mg/kg of body weight) was not effective, but both 20 mg and 40 mg/kg of body weight were found to be effective. The 20 mg/kg of body weight dose was found to be more effective than 40 mg/kg of body weight (the high dose). The administration of ferulic acid to normal rats did not produce any harmful effects. Thus our results show that ferulic acid is an effective anti-hepatotoxic agent without side effects and may be a good candidate in the current search for a natural hepatoprotective agent.

Curcumin influences hepatic expression patterns of matrix metalloproteinases in liver toxicity.

Hepatic fibrosis is a result of an imbalance between enhanced matrix synthesis and diminished breakdown of connective tissue proteins, the net result of which is increased deposition of Extra Cellular Matrix. In this concept Matrix Metalloproteinases play an important role because their activity is largely responsible for extra cellular matrix breakdown. In the present study we have tested the influence of curcumin, the active principle of turmeric, on matrix metalloproteinase expression during alcohol and thermally oxidised sunflower oil induced liver toxicity. Male albino Wistar rats were used for the study. The matrix metalloproteinase expressions were found to be increased significantly in alcohol as well as thermally oxidised sunflower oil groups and on treatment with curcumin there was a significant decrease. In alcohol + thermally oxidised sunflower oil group, we found a significant decrease in matrix metalloproteinase activities. Administration of curcumin significantly improved their activities. From the results obtained, we could conclude that curcumin influences the hepatic matrix metalloproteinases and effectively protects liver against alcohol and delta PUFA induced toxicity.

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.