1993 Fiscal Year Final Research Report Summary
Study on hepatotocicity of p-dichlorobenzene
Project/Area Number |
04680077
|
Research Category |
Grant-in-Aid for General Scientific Research (C)
|
Allocation Type | Single-year Grants |
Research Field |
家政学
|
Research Institution | Kyoto Prefectural University |
Principal Investigator |
MIZUTANI Tamio Kyoto Prefectural University Faculty of Living Science Professor, 生活科学部, 教授 (30046461)
|
Project Period (FY) |
1992 – 1993
|
Keywords | hepatotoxicity / glutathione / rho-dichlorobenzene / phenol-quinone / metabolite |
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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Research Products
(2 results)