Free radical enhancer xenobiotic is an inducer of cataract in rabbit

Free radical enhancers, diquat, paraquat, plumbagin and juglone were used to study the oxy radical-induced damage to the rabbit lens in vitro and in vivo. Each compound caused a 6-8 fold increase in malondialdehyde (MDA) and a 30-55% decrease in reduced glutathione of the lens in vitro. These peroxidative and oxidative changes were potentiated in the presence of 100% O2, abolished by N2 and prevented by desferal-Mn (III) (DF-Mn) or liposomal superoxide dismutase (LSOD) indicating the involvement of O2-. Diquat injected intravitreally as a single dose (300 nmole in 30 microliters of isotonic saline) in the right eye of a 5-wk-old Dutch belted rabbit, induced early cataract after 24-72 h. The lens of the contralateral control eye injected with isotonic saline had no change. In the right eye, O2-. and OH. productions were significantly (P less than 0.01) higher; O2-. was about 16 fold higher in the aqueous humor and vitreous humor, and 5 fold in the lens and retina, and OH. was 35 fold higher in the aqueous humor, 2 fold in vitreous humor and 5 fold in the lens and retina as compared to the respective tissues of the control eye. Enhanced lipid peroxidation in the lens was apparent from the higher levels of MDA and formation of aminophospholipid.MDA Schiff-base conjugates. We propose that cyclic oxidation-reduction of xenobiotics coupled to the endogenous redox systems in the eye, could generate oxy radicals in excessive amounts, triggering cataractogenesis.