EFFECT OF ENDOTOXIN ON HEPATIC MICROSOMAL DRUG METABOLISM OF RATS

Abstract

Infections due to pram-negative bacteria have assumed ever-increasing importance during the past several years. Endotoxin, a soluble lipopolysaccharide cell wall constituent of gram negative bacteria, is released into body fluids during infection by these organisms. A key aspect in the therapeutic management of patients with endotoxemia is the administration of pharmacological agents. Since most drugs are metabolized by the hepatic mixed function oxidase system and/or by conjugation, we studied the effect of intraperitoneally administered endotoxin (a lipopolysaccaride derived from E. Coli 026B6 serotype) on hepatic microsomal drug metabolizing enzymes. Endotoxin dose response studies in adult rats resulted in a striking decrease within 24 hrs postadministration (I.P.) in hepatic microsomal aminopyrine demethylase (51.5%), benzo(a)pyrene hydroxylase (58.9%), and cytochrome P-450 (64.1%) and cytochrome b₅ (90%) of control. These changes occurred with 1 mg/kg but effects were also noted with doses as low as .1 mg/kg. Low protein diet (8%) enhanced the reduction in enzymic activity. Endotoxin administration during late pregnancy also decreased the ability of the rat to metabolize drugs. These studies emphasize the need for careful evaluation of drug administration and effects in patients with endotoxemia.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account

Continue with Google

Continue with ORCiD