The currently available therapies for type 2 diabetes have been unable to achieve normoglycemic status in the majority of patients. The reason may be attributed to the limitations of the drug itself or its side effects. In an effort to develop potent and safe oral antidiabetic agents, we evaluated the in vitro and in vivo hypoglycemic effects of 10 synthetic polyphenolic curcumin analogues on alloxan-induced male diabetic albino rats. In vitro studies showed 7-bis(3,4-dimethoxyphenyl)hepta-1,6-diene-3,5-dione (4) to be the most potential hypoglycemic agent followed by 1,5-bis(4-hydroxy-3-methoxyphenyl)penta-1,4-dien-3-one (10). Structure activity relationship (SAR) of the tested compounds was elucidated and the results were interpreted in terms of in vitro hypoglycemic activities. Furthermore, oral glucose tolerance test (OGTT) with compounds 4, 10 and reference hypoglycemic drug glipizide showed that compound 4 and glipizide had relatively similar effects on the reduction of blood glucose levels within 2 h. Thus, compound 4 might be regarded as a potential hypoglycemic agent being able to reduce glucose concentration both in vitro and in vivo.
Nickel sulfate stimulates inducible nitric oxide synthase (i-NOS) and increases serum nitric oxide concentration by overproduction of reactive nitrogen species due to nitrosative stress. The present study was undertaken to assess possible protective role of L-ascorbic acid as an antioxidant against nickel induced pulmonary nitrosative stress in male albino rats. We studied the effect of the simultaneous treatment with L-ascorbic acid (50 mg/100 g b. wt.; orally) and nickel sulfate (2.0 mg/100 g b. wt.; i.p.) on nitric oxide synthesis by quantitative evaluation of serum i-NOS activities, serum and lung nitric oxide, L-ascorbic acid and protein concentrations of Wistar strain male albino rats. We have further studied histopathological changes in lung tissue after nickel sulfate treatment along with simultaneous exposure of L-ascorbic acid. Nickel sulfate treatment significantly increased the serum i-NOS activity, serum and pulmonary nitric oxide concentration and decreased body weight, pulmonary somatic index, serum and lung L-ascorbic acid and protein concentration as compared to their respective controls. Histopathological changes induced by nickel sulfate showed loss of normal alveolar architecture, inflammation of bronchioles, infiltration of inflammatory cells and patchy congestion of alveolar blood vessels. The simultaneous administration of L-ascorbic acid and nickel sulfate significantly improved all the above biochemical parameters along with histopathology of lung tissues of rats receiving nickel sulfate alone. The study clearly showed a protective role of L-ascorbic acid against nickel induced nitrosative stress in lung tissues.
Nickel sulfate treatment causes testicular oxidative and nitrosative stress in albino rats, but simultaneous supplementation of α-tocopherol was found to be beneficial in combating against such stresses.
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