Potentiation of acetaminophen hepatotoxicity by alcohol
C. J. McClain, J. P. Kromhout, F. J. Peterson and J. L. Holtzman
Severe liver failure developed in three chronic alcoholics after they
ingested acetaminophen for therapeutic reasons. The clinical course was
characterized by SGOT levels of 5,000 to 10,000 IU. Concomitant renal
failure developed in two of these patients, and one died in hepatic coma.
To determine whether alcohol enhances acetaminophen hepatotoxicity, a
lethal dose for 50% survival of a test group (LD50) was performed for mice
fed 10% alcohol in their water supply for three weeks and for mice
receiving a normal diet only. A significant reduction in the LD50 was seen
in the alcohol-pretreated mice, and correlations were noted between
histological findings in the liver and the LD50 data. These findings
suggest that alcohol enhances acetaminophen hepatotoxicity in mice and
provides supportive evidence that these three alcoholic patients probably
had a similar pathophysiological basis for their liver disease.
