Oxidative stress plays a vital role in
diabetic complications. To suppress the oxidative stress mediated damage in diabetic pathophysiology, a special focus has been given on naturally occurring
antioxidants present in normal diet.
D-saccharic acid 1,4-lactone (DSL), a derivative of
D-glucaric acid, is present in many dietary plants and is known for its detoxifying and
antioxidant properties. The aim of the present study was to evaluate the beneficial role of DSL against
alloxan (ALX) induced diabetes in the pancreas tissue of Swiss albino rats. A dose-dependent study for DSL (20-120 mg/kg
body weight) was carried out to find the effective dose of the compound in ALX-induced diabetic rats. ALX exposure elevated the
blood glucose, glycosylated Hb, decreased the plasma
insulin and disturbed the intra-cellular
antioxidant machineries whereas
oral administration of DSL at a dose of 80 mg/kg
body weight restored these alterations close to normal. Investigating the mechanism of the protective activity of DSL we observed that it prevented the pancreatic β-cell apoptosis via mitochondria-dependent pathway. Results showed decreased mitochondrial membrane potential, enhanced
cytochrome c release in the cytosol and reciprocal regulation of Bcl-2 family
proteins in the diabetic rats. These events were also found to be associated with increased level of Apaf-1,
caspase 9, and
caspase 3 that ultimately led to pancreatic β-cell apoptosis. DSL treatment, however, counteracted these changes. In conclusion, DSL possesses the capability of ameliorating the oxidative stress in ALX-induced diabetes and thus could be a promising approach in lessening
diabetic complications.