Antioxidant status in an in vitro model for hyperglycemic lens cataract formation: effect of aldose reductase inhibitor statil.
A decrease in glutathione content followed by a fall in ATP content of lens occurring at approximately 7 days after the onset of diabetes has been demonstrated in an earlier study. This pattern is repeated under more controlled conditions and at shorter time intervals, 24-48 hr, in lenses incubated in vitro under hyperglycemic conditions. Inclusion of aldose reductase inhibitors in the incubation medium not only prevented the accumulation of sorbitol and fructose but also prevented the decrease in glutathione and ATP. It is proposed that the drain on NADPH by the polyol pathway operating at high glucose concentrations results in a perturbation of the system for regenerating reduced glutathione. This aspect of polyol formation is considered to be deleterious to the lens in hyperglycemia, since it may contribute to free radical damage by depressing the system responsible for their removal.
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D002386:Cataract / Q000209:etiology / Q000517:prevention & control*; D005978:Glutathione / Q000032:analysis; D006943:Hyperglycemia / Q000150:complications*; D066298:In Vitro Techniques; D010793:Phthalazines / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D010793:Phthalazines; D011724:Pyridazines; C042829:ponalrestat; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; D005978:Glutathione