MODULATION OF DRUG-METABOLIZING SYSTEMS BY BACTERIAL-ENDOTOXIN IN CARP LIVER AND IMMUNE ORGANS

This report describes a study of the effects of bacterial endotoxin [l ipopolysaccharide (LPS)] on cytochrome P450 levels and ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase (GST) activities in liver and two main immune organs of carp: spleen and head kidney, Als o studied was the paucity of the carp drug-metabolizing system in an e nvironment subject to pollution by a polycyclic aromatic hydrocarbon, 3-methylcholanthrene (3MC), when fish respond to an immune activation by lipopolysaccharide (LPS). In the presence of bacterial endotoxin th e basal cytochrome P450 levels were decreased in liver and spleen. ERO D activity was increased in liver and basal GST activity was increased in spleen. When fish were treated concomitantly with 3MC and LPS, a s uppression of cytochrome P450 induction in liver and head kidney was o bserved. EROD activity induced by 3MC was not modified by administrati on of LPS, GST activity was suppressed by treatment with LPS and induc ing agent in liver and head kidney. In the present study it was found that endotoxin can have profound and differential effects on fish basa l biotransformation of drugs in the liver and immune organs. Also, the induction of biotransformation enzymes by 3MC was modified when fish responded to an immune stimulation. (C) 1998 Academic Press.