Formation of epoxide and quinone protein adducts in B6C3F1 mice treated with naphthalene, sulfate conjugate of 1,4-dihydroxynaphthalene and 1,4-naphthoquinone.
Naphthalene (NA) is metabolically activated to the reactive intermediates, naphthalene oxide (NO) and naphthoquinones. To investigate the role of circulating reactive metabolites in NA toxicity, the half-life of NO was examined. The in vitro half-life of NO in both whole blood and plasma was 10 min. Detectable levels of NO were seen in perfusate leaving the isolated perfused liver of B6C3F1 mice infused with 10 mumol/h NA. Identification of protein sulfhydryl adducts in NA-exposed mice (50 and 100 mg/kg, IP, 24 h) revealed a predominance of quinone adducts in liver, lung, kidney, red blood cells and brain. The epoxide adduct predominated in plasma protein. Administration of the sulfate conjugate of 1,4-dihydroxynaphthalene (NHQS) (100 mg/kg) resulted in formation of naphthoquinone protein sulfhydryl adducts in lung, liver and kidney. Administration of 1,4-naphthoquinone (NQ) (5 mg/kg) produced NQ adducts in liver, lung, kidney, plasma and brain.
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D006207:Half-Life; D006873:Hydroquinones / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D009281:Naphthalenes / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000633:toxicity; D009285:Naphthoquinones / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D006873:Hydroquinones; D009281:Naphthalenes; D009285:Naphthoquinones; C031721:naphthalene; C042033:naphthalene 1,2-oxide; C063601:1,4-naphthohydroquinone; C035342:1,4-naphthoquinone