ANTIOXIDANT AND ANTICATARACTOGENIC EFFECTS OF TOPICAL CAPTOPRIL IN DIQUAT-INDUCED CATARACT IN RABBITS

1-[(2s)-3-Mercapto-2-methylpropionyl]-L-proline (captopril), an antihypertensive and free radical scavenger, protected the rabbit lens from peroxidative and oxidative damage induced by 1 mM diquat in vitro. To evaluate the anticataract efficacy of captopril, an experimental group of five rabbits was treated with topical captopril (1% in 0.15 M NaCl, w/v), and 50-mu-l was instilled onto both eyes four times a day for a total of 8 weeks. Following the same procedure, the eyes of five rabbits were treated with topical 0.15 M NaCl as a control for captopril treatment. At the end of the first week of treatment, a single intravitreal dose of 120 nmole diquat in 30-mu-l of 0.15 M NaCl was injected into the right eye of each rabbit of both the groups. As a control for intravitreal diquat injection, the left eye of all the rabbits were injected with the diluent, 30-mu-l per eye. The intravitreal diquat or its diluent injection was only for one time. From slit-lamp biomicroscopic observation of the diquat-injected right eyes, the anticataract effect of captopril in the treatment group was indicated by the finding that in four of five rabbits the cataract did not advance; whereas in four of five rabbits treated with the diluent the cataract progressed to grade 3. The lenses in the diluent-injected control left eyes of the rabbits treated with the captopril or diluent were normal. However, since the number of animals used for the in vivo studies was few, further confirmation of the anticataract effect of captopril is necessary. In diquat-injected right eyes of animals treated with captopril, the integrated rate of O2- production was about 50% less (p < .001) in the aqueous humor, vitreous humor, and lens, compared with O2-, 33.49 +/- 2.26-mu-M (mean +/- SEM) in the aqueous humor, 17.12 +/- 0.75-mu-M in the vitreous humor, and 31.44 +/- 1.29 nmole/g wet weight in the lens of the diquat-injected right eyes treated with the diluent. Similar significant (p < .01) differences in the production of .OH and H2O2 in eye tissues were also observed. Captopril protected against lipid peroxidation and oxidation of the reduced form of glutathione (GSH) and protein -SH of the lens in diquat-induced cataract in rabbits. It appears that captopril, by acting as an antioxidant in vivo, was able to maintain the diquat-induced altered biochemical parameters in the eye close to normal and retard the progression of oxygen free-radical-triggered cataract in rabbits.