The increase in lipid peroxidation in diabetic rat lens can be reversed by oral sorbinil.
Malondialdehyde (MDA), a product of lipid peroxidation, was measured in the lens of rats in which diabetes had been induced by treatment with streptozotocin (85 mg/kg). The MDA level increases nearly 100% in lenses from diabetic rats, compared with lenses from age-matched control rats. Treating rats with insulin decreases the MDA content of the diabetic rat lens to normal levels. This suggests that the increase in MDA of diabetic rats lens is not due to a toxic effect of streptozotocin, but instead is the result of diabetes mellitus or insulin deficiency. Administration of the aldose reductase inhibitor, sorbinil, decreases lens MDA levels in diabetic rats in a dose-dependent manner with a median effective dose (ED50) of 7.5 mg/kg. This study demonstrates that sorbinil can prevent lipid peroxidation of rat lens resulting from insulin deficiency, which can aid in helping the lens to cope with the oxidative stress of diabetes.
Yeh
L A
LA
Department of Metabolic Diseases, Pfizer Inc., Groton, CT 06340.
Ashton
M A
MA
D000284:Administration, Oral; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D007328:Insulin / Q000494:pharmacology; D007908:Lens, Crystalline / Q000378:metabolism*; D008054:Lipid Peroxides / Q000096:biosynthesis*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D007093:Imidazoles; D048289:Imidazolidines; D007328:Insulin; D008054:Lipid Peroxides; D008315:Malondialdehyde; D000449:Aldehyde Reductase; C026411:sorbinil