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 oxidative breakdown. A significant accumulation of fluorescent 4-hydroxy-2-nonenal-membrane lipid adducts was found in the cells from the old rats. The mechanism mainly responsible for such aldehyde accumulation was shown to be the impairment of its enzymatic metabolism. In fact, while endogenous, that is non-stimulated, aldehyde production was not impaired, the reductive pathway of 4-hydroxy-2-nonenal metabolism in hepatocytes from old rats was strongly depressed. The decrease of 4-hydroxy-2-nonenal consumption with age was confirmed in homogenates from liver and kidney, while there were no differences between young and old animals in heart, lung or brain.