Role of Superoxide Anion Radicals

The discovery that macrophages metabolize ethanol to acetate in vitro may be of importance in understanding the pathogenesis of ethanol-induced tissue damage (1) . When expressed per unit wet weight, the rate of metabolism ofethanol by these cells is comparable to that by hepatocytes (2) . Studies of human and murine macrophages derived from various tissues have revealed that ethanol oxidation by these cells differs markedly from that by hepatocytes in being only slightly inhibited by pyrazole, and therefore, in being largely independent of alcohol dehydrogenase (2-4) . Ethanol oxidation by macrophages was also only slightly impaired by 4-iodopyrazole and 3-amino-1,2,4,-triazole, indicating that it was independent of7r-ADH and catalase . On the other hand, several inhibitors of cytochrome P450 (carbon monoxide, (3-diethylaminoethyl diphenylpropyl acetate, metyrapone, and tetrahydrofurane) markedly suppressed ethanol oxidation, suggesting that macrophages metabolize this alcohol via a cytochrome P450-dependent pathway (2-4) . Since it is known that oxygen-derived free radicals mediate the oxidation of ethanol in certain cell-free in vitro systems (5) and that macrophages are capable of generating large quantities of superoxide radicals (6), the possibility arises that superoxide radicals are involved in ethanol oxidation by macrophages . The present paper describes the results of an investigation into this possibility and demonstrates that a substantial proportion of ethanol oxidation by intact macrophages is superoxide dependent .