Glutathione and mercapturic acid conjugations in the metabolism of naphthalene and 1-naphthyl N-methylcarbamate (carbaryl).
The formation of glutathione (GSH) conjugate in the detoxification of [1-14C]-naphthalene and [naphthyl-14C]-carbaryl was investigated using rat liver homogenate. The mercapturic acid conjugate in rats was also investigated by collection of urine after intraperitoneal injection of 14C substrates. The formation of water-soluble metabolites in vitro from naphthalene was dependent on the amount of glutathione added, but this was not seen in carbaryl metabolism. In vitro, the metabolism of [1-14C]-naphthalene produced 50% GSH conjugates in the incubation mixture, whereas in vivo the metabolism of this compound produced 65% mercapturic acid conjugate in the urine. There was no evidence of GSH or mercapturic acid conjugate in the metabolism of [naphthyl-14C]-carbaryl in vitro and in vivo. This conclusion was made by comparing the nature and chemical characteristics of GSH and mercapturic acid conjugates formed in [1-14C]-naphthalene metabolism. With the aid of the specific enzyme (e.g. beta-glucuronidase and sulfatase) and acid hydrolysis, the water-soluble metabolites of [naphthyl-14C]-carbaryl were tentatively recognized as glucuronide or sulfate conjugated mainly with 5,6-dihydro-5,6-dihydroxycarbaryl or N-hydroxy-methyl carbaryl and their hydrolytic products. This data demonstrated that the substituent group on the naphthalene molecule may affect the significance of GSH conjugation.
D000111:Acetylcysteine / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D012721:Carbaryl / Q000378:metabolism*; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006868:Hydrolysis; D066298:In Vitro Techniques; D008658:Inactivation, Metabolic; D008862:Microsomes, Liver / Q000378:metabolism; D009281:Naphthalenes / Q000378:metabolism*; D051381:Rats
D009281:Naphthalenes; D005978:Glutathione; D012721:Carbaryl; D000111:Acetylcysteine