Free radical generation by neutrophils: a potential mechanism of cellular injury in acute alcoholic hepatitis

Abstract

Liver membrane vesicles were prepared from operative liver biopsies from six patient volunteers undergoing abdominal surgery for non-hepatic disease. Neutrophils were extracted from their blood. The liver membrane vesicles were exposed to 1 mmol/l acetaldehyde with or without reduction of the resultant adducts formed. The production of superoxide anion by the neutrophils upon exposure to the liver membrane vesicles prepared from the same patient was assessed by measuring the rate of cytochrome c reduction before and after the addition of superoxide dismutase. Preincubation with acetaldehyde significantly increased superoxide production in response to both the reduced (from 35.5 +/- 7.1 nmol O2-/10(8) cells/min to 128 +/- 25, mean +/- SEM, p less than 0.01) and the non-reduced liver cell membranes (from 17.2 +/- 4.3 to 81 +/- 17, p less than 0.01); 1 mmol/l acetaldehyde alone caused no superoxide production. Neutrophil free radical production in response to acetaldehyde altered hepatocyte membranes could be an important mechanism of cellular injury in acute alcoholic hepatitis.