title: Hepatotoxicity of eugenol and related compounds in mice depleted of glutathione: structural requirements for toxic potency.
abstract: Eugenol produces hepatic injury in mice depleted of glutathione (GSH) by pretreatment with buthionine sulfoximine (BSO). Several eugenol analogs were examined for their ability to cause hepatic injury after administration to mice in combination with BSO. Hepatotoxicity was assessed by measuring relative liver weight, liver blood volume, and serum GPT activity in mice. Comparison 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 formed by metabolic oxidation of eugenol plays a role in inducing hepatotoxicity in GSH-depleted mice.
authors.affiliation: Department of Food Science and Nutrition, Kyoto Prefectural University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mizutani
authors.forename: K
authors.initials: K
authors.lastname: Satoh
authors.forename: H
authors.initials: H
authors.lastname: Nomura
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D019328:Buthionine Sulfoximine; D005054:Eugenol / Q000633:toxicity*; D005978:Glutathione / Q000172:deficiency*; D008099:Liver / Q000187:drug effects*; D008297:Male; D008717:Methionine Sulfoximine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity; D051379:Mice; D008815:Mice, Inbred Strains; D013329:Structure-Activity Relationship
chemical_list: D008717:Methionine Sulfoximine; D005054:Eugenol; D019328:Buthionine Sulfoximine; D000410:Alanine Transaminase; D005978:Glutathione