Biomaterial Database

Hepatotoxicity of eugenol in mice depleted of glutathione by treatment with DL-buthionine sulfoximine. 1991

T Mizutani, and K Satoh, and H Nomura, and K Nakanishi

Department of Food Science and Nutrition, Kyoto Prefectural University, Japan.

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 sulfoximine (BSO; 1 hr before eugenol, 4 mmol/kg, ip) developed hepatotoxicity characterized by increases in relative liver weight and serum GPT, hepatic congestion, and centrilobular necrosis of hepatocytes. Eugenol (up to 600 mg/kg) alone produced no hepatotoxicity. Drug metabolism inhibitors such as carbon disulfide, methoxsalen, and piperonyl butoxide prevented or significantly reduced the hepatotoxic effect of eugenol given in combination with BSO. On the other hand, pretreatment with phenobarbital (PB) increased the hepatotoxicity. 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 by BSO treatment.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008102	Liver Circulation	The circulation of BLOOD through the LIVER.	Hepatic Circulation,Circulation, Liver,Circulation, Hepatic
D008297	Male		Males
D008717	Methionine Sulfoximine		Sulfoximine, Methionine
D008815	Mice, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.	Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D009929	Organ Size	The measurement of an organ in volume, mass, or heaviness.	Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D010634	Phenobarbital	A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.	Phenemal,Phenobarbitone,Phenylbarbital,Gardenal,Hysteps,Luminal,Phenobarbital Sodium,Phenobarbital, Monosodium Salt,Phenylethylbarbituric Acid,Acid, Phenylethylbarbituric,Monosodium Salt Phenobarbital,Sodium, Phenobarbital
D005054	Eugenol	A cinnamate derivative of the shikimate pathway found in CLOVE OIL and other PLANTS.	Phenol, 2-methoxy-4-(2-propenyl)-
D005978	Glutathione	A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.	Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D000410	Alanine Transaminase	An enzyme that catalyzes the conversion of L-alanine and 2-oxoglutarate to pyruvate and L-glutamate. (From Enzyme Nomenclature, 1992) EC 2.6.1.2.	Alanine Aminotransferase,Glutamic-Pyruvic Transaminase,SGPT,Alanine-2-Oxoglutarate Aminotransferase,Glutamic-Alanine Transaminase,Alanine 2 Oxoglutarate Aminotransferase,Aminotransferase, Alanine,Aminotransferase, Alanine-2-Oxoglutarate,Glutamic Alanine Transaminase,Glutamic Pyruvic Transaminase,Transaminase, Alanine,Transaminase, Glutamic-Alanine,Transaminase, Glutamic-Pyruvic