1991 Fiscal Year Final Research Report Summary
Toxicity and Metabolism of Eugenol, a Food Additive
Project/Area Number |
02680068
|
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, Department of Living Science, Professor, 生活科学部, 教授 (30046461)
|
Project Period (FY) |
1990 – 1991
|
Keywords | Buthionine sulfoximine / Eugenol / Glutathione / Hepatotoxicity / Metabolic activation / Mouse |
Research Abstract |
Eugenol is widely used as a food flavoring agent and a dental analgesic. Mice treated with eugenol(400-600 mg/kg, po)in combination with an inhibitor of glutathione(GSH)synthesis, buthionine sufoximine(BSO ; 4 mmol/kg, ip)developed hepatotoxicity characterized by increases in relative liver weight and serum GPT, hepatic congestion, and necrosis of hepatocytes. Drug metabolism inhibitors such as carbort disulfide and methoxsalen prevented the hepatotoxic effect of eugenol given in combination with BSO. These results suggest that eugenol is activated by a cytochrome-P-450-dependent metabolic reaction and that the liver injury is caused by inadequate rates of detoxification of the resulting metabolite in mice depleted of hepatic GSH. Several eugenol analogs such as safrole and chavibetol were examinedfor their ability to cause hepatic injury in GSH-depleted mice. Comp ; Wrison of the tested compounds showed that the structural requirements for toxic potency was a phenolic ring having an allyl substituent at the 4-position. These structural. requirements can be explained by assuming that a vinylogous quinone methide tonned by metabolic oxidation of eugenol plays a role in inducing hepatotoxicity.
|
Research Products
(4 results)