Effect of decreased glucuronidation and sulfation on covalent binding of naphthalene in isolated rat hepatocytes.
Isolated hepatocytes metabolize naphthalene to water soluble compounds. During metabolism, reactive intermediates are formed which bind irreversibly to cellular macromolecules. When naphthalene concentrations in the incubation were raised from 400 to 1200 microM the formation of water soluble metabolites of the aromatic hydrocarbon increased about twice from 16 to 37 nmol/mg cellular protein X h, whereas covalent binding increased up to 10 times. This suggests a qualitative shift in the metabolic pattern of naphthalene probably due to the exhaustion of inactivating pathways. Inhibition of glucuronidation and sulfation -- 2 reactions involved in the metabolism of naphthalene -- did not change the amount of water soluble metabolites but dramatically increased binding.
D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D005965:Glucuronates / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D009281:Naphthalenes / Q000378:metabolism*; D051381:Rats; D013464:Sulfuric Acids / Q000378:metabolism
D005965:Glucuronates; D009281:Naphthalenes; D013464:Sulfuric Acids