| The role of increased lipid peroxidation (LP) as the operative mechanism in the early and later stages in the development of alcoholic liver injuries and cancer were investigated. Adult male rats were fed liquid diets containing 36% as ethanol derived calories, with cod liver oil substituting for corn oil, olive oil and cotton seed oil (n-6 fatty acid) for 28 days or 18 months. Control rats received similar diets supplemented with vitamin E. Indices of increased LP including elevated hepatic conjugated dienes, lipid fluorescence, malondialdehyde and ethane exhalation were observed in rats fed ethanol and cod liver oil. These changes were significantly reduced by supplemental vitamin V. Similarly, changes in major components of the membrane lipids, peroxidation of hepatic PUFA and depleted levels of hepatic vitamin A and E were partially reversed in the vitamin E supplemented animals. Thus, increased LP, attenuated by dietary vitamin E, is an attendant mechanism in alcoholic liver injury. In other experiments, female C57BL/6 mice were treated with or without ethanol, cocaine, LP-BM5 murine leukemia retrovirus, low protein diets, methylbenzylnitrosamine and supplemental vitamin E. Ethanol suppressed the numbers of T-cell, macrophages and increased the accumulation of indices of increased LP. Significant increases in T-subsets, B-cells and macrophages were observed in the retrovirus infected animals. These changes were further exacerbated in the virus infected animals exposed to ethanol. Similarly, exposure to ethanol in cocaine treated animals synergistically increased cocaine-induced lipid peroxidation. Furthermore, increased products of LP and severe liver pathologic damages were seen in immunocompromised animals fed low levels of dietary protein treated with cocaine. Additionally, exposure to ethanol promoted the size and frequency of chemically-induced esophageal preneoplastic tumor via an attendant increased LP. Supplemental dietary vitamin E reduced the indices of LP and the size and frequency of the preneoplastic tumors.;Thus, increased LP, attenuated by dietary vitamin E, is an attendant mechanism in the complex process of carcinogenesis induced by a chemical carcinogen, and promoted by ethanol, protein malnutrition and retrovirus infection. |
