Effects of Intravenous and Intracutaneous Bacillus Calmette-Guérin Application on the Drug-Metabolizing System of the Liver

Abstract

Both single intravenous and repeated intracutaneous injections of bacillus Calmette-Guérin (BCG) resulted in alteration of the hepatic microsomal drug-metabolizing enzymes of the rat liver. The cytochrome P-450 content was not significantly altered; its activity (ethoxycoumarin O-dealkylation) was inhibited in both the intravenous and intracutaneous group. The arylhydrocarbon-hydroxylase and aminopyrine-demethylase activities were also diminished; decrease of cytochrome-c-reductase activity was noted after intravenous application only. Comparison of the results for the intravenous and intracutaneous application routes respectively showed qualitative and quantitative differences. The inhibitory effects of BCG treatment on the drug-metabolizing enzymes of the rat liver can only partly be explained by changes in the cytochrome P-450 system. These findings might lead to reconsideration of dosage of drugs in cancer (malignant melanoma) patients treated by combined chemoimmunotherapy.

Effect of murine schistosomiasis on hepatic cytochrome P‐450 and microsomal protein

“…These inflammatory mediators released from granulomatous reaction inhibit the de novo synthesis of enzymes in the endoplasmic reticulum of the hepatocytes. This is consistent with previous work where BCG significantly reduced drug biotransformation in animals (14,15). Moreover, Farguhar et al suggested that granulomatous reaction is an important factor for this reduction in cytochrome P-450 and microso-ma1 enzyme level (1 5).…”