Endotoxin and low protein diet induced depression of the rat hepatic drug metabolism.

The effects of the combination of low protein diet feeding and endotoxin (E. coli, serotype 026 B6) upon rat hepatic microsomal mixed function oxidase (MFO) enzymes were investigated. Short-term (7 days) feeding of low protein (8%) diet and acute (single dose) exposure to endotoxin resulted in an additive decrease in MFO enzymes. However, chronic (7 days) endotoxin exposure did not depress liver microsomal MFO enzyme activities except for aniline hydroxylase. Long-term (105 days) feeding of the low protein diet and acute endotoxin exposure further decreased aminopyrine N-demethylase and benzo(a)pyrene hydroxylase activities compared to individual treatments. These results suggest that, under these experimental conditions, the two host-related environmental factors interact and potentiate a decrease in rat hepatic microsomal drug metabolizing enzymes. These observations may be of clinical relevance to explain altered drug reactions in patients with gram-negative infections and endotoxemia under the conditions of malnutrition.