Induction of hepatic microsomal drug-metabolizing enzymes by methylsulphonyl metabolites of polychlorinated biphenyl congeners in rats

Add time:08/01/2019    Source:sciencedirect.com

The effect of methylsulphonyl (MeSO2) metabolites of 2,3′,4′,5-tetrachlorobiphenyl (tetraCB) (IU-70), 2,2′,3′,4′,5-pentachlorobiphenyl (pentaCB) (IU-87), 2,2′,4′,5,5′ -pentaCB (IU-101) and 2,2′,3′,4′,5,5′-hexachlorobiphenyl (hexaCB) (IU-141), on the hepatic microsomal drug-metabolizing enzyme system was investigated in rats. The administration of 3-MeSO2-2,3′,4′,5-tetraCB (10 μmol/kg), 3-MeSO2-2,2′,3′,4′,5-pentaCB (0.5 μmol/kg), 3-MeSO2-2,2′,4′,5,5′-pentaCB (0.5 μmol/kg) and 3-MeSO2-2,2′,3′,4′,5,5′-hexaCB (2 μmol/kg) to rats significantly increased the contents of cytochromes P-450 and b5 and the activities of aminopyrine N-demethylase, 7-ethoxycoumarin O-deethylase and benzo[a]pyrene hydroxylase. From these results, it is suggested that the 3-MeSO2 derivatives studied are possibly potent phenobarbital-like inducers of microsomal drug-metabolizing enzymes. On the other hand, 4-MeSO2-2,3′,4′,5-tetraCB, 4-MeSO2-2,2′,3′,4′,5-pentaCB, 4-MeSO2-2,2′, 4′,5,5′-pentaCB and 4-MeSO2-2,2′,3′,4′,5,5′-hexaCB had almost no effect on both cytochrome contents and these enzyme activities. After 96 h, following administration of 2,3′,4′,5-tetraCB, 2,2′,3′,4′,5-pentaCB, 2,2′,4′,5,5′-pentaCB and 2,2′,3′,4′,5,5′-hexaCB

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