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The increase in lipid peroxidation in diabetic rat lens can be reversed by oral sorbinil
1Department of Metabolic Diseases, Pfizer Inc., Groton, CT 06340.
Abstract:
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.
Insights
Diabetic rats show increased lipid peroxidation in their lenses. Insulin treatment and sorbinil, an aldose reductase inhibitor, effectively reduced this malondialdehyde (MDA) increase, mitigating oxidative stress in the diabetic lens.
Area of Science:
- Biochemistry
- Ophthalmology
- Endocrinology
Background:
- Diabetes mellitus is associated with increased oxidative stress.
- Lipid peroxidation, measured by malondialdehyde (MDA), is a key indicator of oxidative damage.
- The lens is particularly vulnerable to oxidative stress in diabetic conditions.
Purpose of the Study:
- To investigate the effect of diabetes-induced insulin deficiency on lipid peroxidation in rat lenses.
- To evaluate the potential of insulin and aldose reductase inhibitors to counteract this oxidative damage.
Main Methods:
- Diabetes was induced in rats using streptozotocin.
- Malondialdehyde (MDA) levels were measured in rat lenses.
- Rats were treated with insulin or the aldose reductase inhibitor sorbinil.
Main Results:
- Diabetic rat lenses showed a nearly 100% increase in MDA levels compared to controls.
- Insulin treatment normalized MDA levels in diabetic rat lenses.
- Sorbinil administration dose-dependently decreased lens MDA levels, with an ED50 of 7.5 mg/kg.
Conclusions:
- The increase in lens MDA in diabetes is due to insulin deficiency, not streptozotocin toxicity.
- Sorbinil effectively prevents lipid peroxidation in the diabetic rat lens.
- Aldose reductase inhibition may be a therapeutic strategy to manage diabetic lens complications by reducing oxidative stress.