METABOLISM OF 4-HYDROXY-2-NONENAL AND AGING

Hepatocytes isolated from male Wistar rats of 2-3 and 20-24 months of age were compared as regards concentration and metabolism of 4-hydroxy -2-nonenal, one of the major aldehyde products of n-6 fatty acid oxida tive breakdown. A significant accumulation of fluorescent 4-hydroxy-2- nonenal-membrane lipid adducts was found in the cells from the old rat s. The mechanism mainly responsible for such aldehyde accumulation was shown to be the impairment of its enzymatic metabolism. In fact, whil e endogenous, that is non-stimulated, aldehyde production was not impa ired, the reductive pathway of 4-hydroxy-2-nonenal metabolism in hepat ocytes from old rats was strongly depressed. The decrease of 4-hydroxy -2-nonenal consumption with age was confirmed in homogenates from live r and kidney, while there were no differences between young and old an imals in heart, lung or brain. (C) 1995 Academic Press, Inc.