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CAN NITRIC OXIDE‐GENERATING COMPOUNDS IMPROVE THE OXIDATIVE STRESS RESPONSE IN EXPERIMENTALLY DIABETIC RATS?
Author(s) -
Mohamadin Ahmed MA,
Hammad Lamiaa NA,
ElBab Mohamed Fath,
Gawad Hala S Abdel
Publication year - 2007
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2007.04622.x
Subject(s) - tbars , endocrinology , medicine , chemistry , glutathione peroxidase , glibenclamide , oxidative stress , diabetes mellitus , glutathione , nitric oxide , sodium nitroprusside , lipid peroxidation , superoxide dismutase , biochemistry , enzyme
SUMMARY1 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 were 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.