| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1993: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1992: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
rho-Dichlorobenzene (rho-DCB) is widely used as a moth repellent, and a space deodorant. In mice pretreated with DL-buthionine sulfoximine (BSO ; 2mmol/kg or higher doses, i, p.), an inhibitor of glutathione (GSH) synthesis, administration of rho-DCB (100-400mg/kg, p.o.) resulted in dose-dependent hepatotoxicity as judged by increased serum alanine aminotransferase (ALT) activities and liver calcium concentrations and by histologic examination of the liver. rho-DCB alone (up to 1200mg/kg) resulted in no hepatotoxicity. Administration of GSH monoethyl ester, which is known as a useful means for increasing organ GSH levels, protected against the hepatotoxicity caused by rho-DCB in combination with BSO.Treatment with inhibitors of hepatic cytochrome rho-450-dependent monooxygenases, carbon disulfide, metyrapone, and piperonyl butoxide, also prevented the hepatotoxicity. These results suggest that rho-DCB is activated by a cytochrome rho-450-dependent metabolic reaction and that the hepatotoxicity is caused by inadequate rates of detoxification of the resulting metamolite in mice depleted of hepatic GSH by BSO treatment. The liver injury was preceded by an extensive depletion of hepatic GSH but not accompanied by significant changes in hepatic contents of lipid peroxides and protein thiols.
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