Can nitric oxide-generating compounds improve the oxidative stress response in experimentally diabetic rats?
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.
Mohamadin
Ahmed M A
AM
Biochemistry Department and Tumor Marker Oncology Research Unit, Faculty of Pharmacy Boy, Al-Azhar University, Cairo, Egypt. amohamadin@yahoo.com
Hammad
Lamiaa N A
LN
El-Bab
Mohamed Fath
MF
Gawad
Hala S Abdel
HS
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001120:Arginine / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D006442:Glycated Hemoglobin / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D016014:Linear Models; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology* / Q000627:therapeutic use; D009599:Nitroprusside / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D001120:Arginine; D001786:Blood Glucose; D002374:Catalase; D005978:Glutathione; D005979:Glutathione Peroxidase; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008055:Lipids; D009569:Nitric Oxide; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D013482:Superoxide Dismutase