Cataractogenicity and bioactivation of naphthalene derivatives in lens culture and in vivo.
The cataractogenicity of naphthalene derivatives was investigated in a lens culture system that included the lens with an intact capsule and epithelium. The in vivo cataractogenicity of naphthalene, 1000 or 2000 mg/kg ip, also was evaluated in New Zealand white and Chinchilla pigmented rabbits. A dose-related brunescence was observed in lenses incubated with 1,4-naphthoquinone in concentrations from 31.6 to 316 microM. With 316 microM naphthoquinone, lenses were totally opaque within 24 hr. No lenticular opacities were observed with 1-naphthol or 2-naphthol in incubations lasting up to 96 hr. The bioactivation of naphthalene derivatives to reactive free radical intermediates by lenses in organ culture was investigated by electron spin resonance spectrometry (ESR) using the spin trap alpha-phenyl-N-t-butylnitrone (PBN). Lenses were incubated with 316 microM naphthoquinone and 100 mM PBN for 0.25, 4 or 7 hr. A spin trapped radical product with unresolved peaks was observed with 0.25 and 7 hr incubation. No radicals were detected in the 4 hr incubation, nor in control cultures lacking either the lens, naphthoquinone or PBN. In the in vivo studies, naphthalene was cataractogenic in both albino and pigmented rabbits. The in vitro results indicate that naphthoquinone can be bioactivated by rabbit lens to a reactive free radical intermediate, which may contribute to cataractogenicity.
Lubek
B M
BM
Faculty of Pharmacy, University of Toronto, Ontario, Canada.
Kubow
S
S
Basu
P K
PK
Wells
P G
PG
D000818:Animals; D001711:Biotransformation; D002386:Cataract / Q000139:chemically induced*; D003497:Cyclic N-Oxides; D005609:Free Radicals; D007908:Lens, Crystalline / Q000187:drug effects* / Q000201:enzymology; D009281:Naphthalenes / Q000493:pharmacokinetics / Q000633:toxicity*; D009589:Nitrogen Oxides; D009924:Organ Culture Techniques; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013113:Spin Labels
D003497:Cyclic N-Oxides; D005609:Free Radicals; D009281:Naphthalenes; D009589:Nitrogen Oxides; D013113:Spin Labels; C029217:phenyl-N-tert-butylnitrone; D000254:Sodium-Potassium-Exchanging ATPase