Dietary grapes (Vitis vinifera) feeding attenuates ethanol-induced oxidative stress in blood and modulates immune functions in mice.

Ethanol metabolism is known to induce overwhelming production of reactive oxygen species (ROS) and also to cause associated immune dysfunction. Several interventional agents of plant origin, in particular fruits and vegetables have been used to counteract these alterations induced by ethanol. In this study, we investigated the efficacy of dietary feeding of skin and flesh of grapes (Vitis vinifera L.) on the alterations in immune and vascular functions in mice with liver abnormalities induced by chronic ethanol consumption. Results revealed that feeding of both grape skin and flesh (2.5 g/kg body wt/day) effectively attenuated the oxidative stress and alterations in immune function and angiogenesis induced by chronic ethanol consumption (1.6 g/kg body wt/day for 12 weeks) in mice. The antioxidant actions of the grape skin and flesh as observed in this study might be attributed to the polyphenols present in the grapes.

Effects of long-term ethanol consumption on adhesion molecules in liver.

Adhesion molecules play an important role in the pathogenesis of several diseases. In this study, expression of adhesion molecules was examined in the setting of chronic alcohol induced liver damage of male albino Wistar strain rats (16-18 weeks-old, 200-220 g) in a time dependent manner. Decreased protein level and increased activities of liver marker enzymes in response to the chronic ethanol (1.6 g ethanol/kg body weight/day) exposure, indicated that these animals suffered from liver damage in a time-dependent manner. Flow cytometric analysis revealed that chronic ethanol treatment induced intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and platelet endothelial cell adhesion molecule-1 expression in liver tissues of rats with duration of ethanol exposure. The results suggest that the adhesion molecules may be associated with the initiation of hepatic injury during alcohol intoxication.

Protective effect of resveratrol and vitamin E against ethanol-induced oxidative damage in mice: Biochemical and immunological basis.

The metabolism of ethanol gives rise to the generation of excess amounts of reactive oxygen species and is also associated with immune dysfunction. We examined the efficacy of resveratrol and vitamin E on the immunomodulatory activity and vascular function in mice with liver abnormalities induced by chronic ethanol consumption by measuring the protein, liver-specific transaminase enzymes, antioxidant enzymes and non-enzymes such as reduced glutathione (GSH) content, thiobarbituric acid reactive substance (TBARS) level, nitrite level, and activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GPx) and glutathione-S-transferase (GST), and cytokines such as interleukin (IL)-2, IL-4, IL-10, tumor necrosis factor (TNF)-, gamma interferon (IFN-), vascular endothelial growth factor (VEGF)-A and transforming growth factor (TGF)-1 in mice blood. Ethanol (1.6 g/kg body wt/day) exposure for 12 wks significantly increased TBARS and nitrite levels and GST activity, and significantly decreased GSH content and the activities of SOD, CAT, GR and GPx in whole blood hemolyzate of 8-10 wks-old male BALB/c mice (weighing 20-30 g). Ethanol exposure also elevated the activities of transaminase enzymes (AST and ALT), IL-10, TNF-, IFN-, VEGF-A and TGF-1, while decreasing the albumin concentration and IL-4 activity in the serum. Both resveratrol (5 mg kg-1 day-1) and vitamin E (80 mg kg-1 day-1) treatment significantly reduced AST, ALT, GST, IL-10, TNF-, IFN-, VEGF-A and TGF-1 activities and levels of TBARS and nitrite, and elevated albumin content, GSH level and activities of SOD, CAT, GR and GPx, compared to ethanol-treated group. Thus, results from the study demonstrated that both resveratrol (5 mg kg-1 day-1) and vitamin E (80 mg kg-1 day-1) can effectively ameliorate ethanol (1.6 g kg-1 day-1)-induced oxidative challenges, immunomodulatory activity and angiogenesis processes.

Time-dependent effects of ethanol on blood oxidative stress parameters and cytokines.

Alcohol consumption is implicated in the genesis of a spectrum of liver abnormalities, which are associated with a number of factors. In the present study, time-dependent effects of ethanol on cytokines (TNF-alpha, IL-2, IL-4, IL-10, IFN-gamma, VEGF-A and TGF-beta1) in serum, and blood oxidative stress parameters such as reduced glutathione content, TBARS level and activities of GPx, GR, GST, catalase and SOD in 8-10 weeks-old male BALB/c mice have been investigated. Ethanol administered @ 1.6 g/kg body wt/day significantly increased the activities of liver marker enzymes AST, ALT and ALP. Serum nitrite levels and haemolysate TBARS level also increased, while total antioxidant status in serum and GSH content in whole blood hemolysate decreased from 4th week onwards of exposure. In spite of the increased serum nitrite level and GST activity in the haemolysate, albumin level in serum, GPx and GR activities in haemolysate decreased after 12 weeks of exposure. Chronic ethanol treatment did not show any effect on IL-2, but IL-4 level was reduced and other cytokines such as IL-10, TNF-alpha, IFN-gamma, TGF-beta1 and VEGF-A levels were increased significantly after 12 weeks. The study indicates a relationship between free radical generation and immune response, and suggests that ethanol-induced liver damage is associated with oxidative stress and immunological alterations in a time-dependent manner.