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Hepatic and extrahepatic metabolism of 14C-styrene oxide
Abstract:
With 8-(14)C-styrene oxide as substrate, specific glutathione S-transferase and epoxide hydrase activities were determined in subcellular fractions of liver, lungs, kidney, and intestinal mucosa from rabbit, rat, and guinea pig. Liver had the highest enzyme activities in each species. Rat and guinea pig had higher glutathione S-transferase activity in both liver and kidney than rabbit. Rat testis also had appreciable glutathione S-transferase activity. The perinatal development of epoxide hydrase and glutathione S-transferase was followed in liver and several extrahepatic tissues of fetal and neonatal guinea pigs and rabbits. The rates at which enzyme activities reached adult levels in the extrahepatic tissues differed from the liver in both species. Epoxide hydrase and glutathione S-transferases developed at different rates in each organ, demonstrating that the relative importance of these two detoxifying pathways for styrene oxide may shift before and after birth. The effects of pretreating male and female rats with phenobarbital (PB), 1,2,3,4-dibenzanthracene (DBA), pregnenolone-16alpha-carbonitrile (PCN), or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on hepatic and extrahepatic epoxide hydrase and glutathione S-transferase activities toward styrene oxide were determined. PB increased both enzyme activities in liver of both sexes. PCN induced only glutathione S-transferase activity in female liver. Extrahepatic epoxide hydrase and glutathione S-transferase activities were unaffected except that TCDD doubled female renal epoxide hydrase activity and PB increased intestinal epoxide hydrase activity in both sexes. Styrene oxide biotransformation was studied in isolated, perfused rat liver and rabbit lung preparations. Conjugation with glutathione was a major metabolic pathway although significant amounts of diol were also formed in each instance. In rat liver, 27-40% of the administered styrene oxide was excreted via the bile mainly as S-(1-phenyl-2-hydroxyethyl)glutathione.