Effect of polybrominated biphenyls, beta-naphthoflavone and phenobarbital on arylhydrocarbon hydroxylase activities and chloroform-induced nephrotoxicity and hepatotoxicity in male C57BL/6J and DBA/2J mice.
Administration of chloroform (CHCl3) to male C57/6J (C57) and DBA/2J (DBA) mice produced dose-dependent hepatic and renal damage. Hepatic arylhydrocarbon hydroxylase (AHH) activity was higher in C57 than DBA mice; in kidney, AHH activity was higher in DBA than in C57 mice. CHCl3 caused the same degree of liver damage in both strains of mice; however, nephrotoxicity of CHCl3 was greater in DBA than in C57 mice. Pretreatment of C57 and DBA mice with phenobarbital (PB) markedly increased hepatic AHH activity and hepatotoxicity of CHCl3 in both strains but did not affect renal AHH or nephrotoxicity of CHCl3. Similarly, beta-naphthoflavone (BNF) enhanced AHH activity and CHCl3 hepatotoxicity in C57 mice, but had little effect on nephrotoxicity. BNF did not affect hepatic AHH nor CHCl3-induced hepatic injury in male DBA mice. Pretreatment with polybrominated biphenyl (PBB) enhanced AHH activity in liver and CHCl3 hepatotoxicity in both strains. After PBB, nephrotoxicity of CHCl3 and renal AHH activity were increased in C57 mice whereas PBB did not alter nephrotoxicity or renal AHH in DBA mice. These results suggest that CHCl3-nephrotoxicity is independent of hepatotoxicity.
D000410:Alanine Transaminase / Q000032:analysis; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000032:analysis*; D001571:Benzoflavones / Q000494:pharmacology*; D001806:Blood Urea Nitrogen; D002725:Chloroform / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010634:Phenobarbital / Q000494:pharmacology*; D011075:Polybrominated Biphenyls / Q000494:pharmacology*; D013045:Species Specificity; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D005419:Flavonoids; D011075:Polybrominated Biphenyls; D019324:beta-Naphthoflavone; D002725:Chloroform; D001189:Aryl Hydrocarbon Hydroxylases; D000410:Alanine Transaminase; D010634:Phenobarbital