Can nitric oxide-generating compounds improve the oxidative stress response in experimentally diabetic rats?

Ahmed M A Mohamadin, Lamiaa N A Hammad, Mohamed Fath El-Bab, Hala S Abdel Gawad
Clinical and Experimental Pharmacology & Physiology 2007, 34 (7): 586-93
1. The present study was designed to evaluate the protective effects of the nitric oxide (NO)-generating compounds L-arginine (L-Arg) and sodium nitroprusside (SNP) on oxidative stress markers in streptozotocin (STZ)-diabetic rats. 2. Diabetes was induced after a single intraperitoneal injection of STZ (60 mg/kg). Rats were divided into non-diabetic (control), diabetic and treated diabetic groups. The treated diabetic groups were supplemented with L-Arg (300 mg/kg), SNP (3 mg/kg per day) or glibenclamide (0.6 mg/kg per day) orally for 4 weeks. 3. At the end of the experiment, fasted rats were killed by cervical decapitation. Blood was collected for estimation of glucose, haemoglobin, glycosylated haemoglobin (HbA(1c)), total cholesterol, high-density lipoprotein-cholesterol and triglycerides. Thiobarbituric acid-reactive substances (TBARS; an index of lipid peroxidation), superoxide dismutase, glutathione peroxidase, catalase, nitrate/nitrite (NO(x)) and reduced glutathione (GSH) were estimated in liver and kidney homogenates. 4. A significant increase was observed in plasma glucose levels and HbA(1c), with a concomitant decrease in haemoglobin levels, in diabetic rats. These alterations reverted back to near normal after treatment with the NO-generating compounds. A loss of bodyweight, polydipsia, polyphagia and elevated levels of serum cholesterol and triglycerides were observed in diabetic rats. Hyperglycaemia was accompanied by a significant increase in tissue TBARS and a decrease in NO(x), GSH and anti-oxidant enzymes, whereas, supplementation with L-Arg and SNP significantly reduced TBARS levels and increased GSH and anti-oxidant enzyme activities. Linear regression analysis indicated that blood glucose and TBARS had a significant positive correlation with HbA(1c), whereas a negative correlation was observed between GSH and NO(x). 5. It is concluded that NO-generating compounds improve most of the biochemical abnormalities and anti-oxidant levels in diabetic rats. The beneficial effects of NO-generating compounds can be attributed to the generation of NO and/or enhanced anti-oxidant enzyme activities.

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