LIPID-PEROXIDATION PRODUCTS AND ANTIOXIDANTS IN HUMAN-DISEASE

Lipid peroxidation (LPO) is a free radical-related process that in bio logic systems may occur under enzymatic control, e.g., for the generat ion of lipid-derived inflammatory mediators, or nonenzymatically. This latter form is associated mostly with cellular damage as a result of oxidative stress, which also involves cellular antioxidants in this pr ocess. This article focuses on the relevance of two LPO products, malo ndialdehyde (MDA) and 4-hydroxynonenal (HNE), to the pathophysiology o f human disease. The former has been studied in human serum samples of hepatitis C virus-infected adults and human immunodeficiency virus-in fected children. In these two cases it is shown that the specific assa y of serum MDA is useful for the clinical management of these patients . The presence of MDA in subretinal fluid of patients with retinal det achment suggests the involvement of oxidative stress in this process. Moreover, we were able to report the dependence of this involvement on the degree of myopia in these patients. The assay of MDA contents in the peripheral nerves of rats fed a chronic alcohol-containing diet or diabetic mice also confirms the pathophysiologic role of oxidative st ress in these experimental models. In these two cases, associated with an increase in tissue LPO products content, we detected a decrease of glutathione peroxidase (GSHPx) activity in peripheral nerve, among ot her modifications. We have demonstrated that in vitro HNE is able to i nhibit GSHPx activity in an apparent competitive manner, and that glut athione may partially protect and/or prevent this inactivation. The ac cumulation of LPO products in the brain of patients with Alzheimer's d isease has also been described, and it is on the basis of this observa tion that we have tried to elucidate the role of oxidative stress and cellular antioxidants in beta-amyloid-induced apoptotic cell death of rat embryo neurons. Finally, we discuss the possible role of the obser ved vascular effects of HNE on human arteries.