Affiliation:
1. Shri Neminath Jain Brahmacharyashram Trust's, Shreeman Sureshdada Jain College of Pharmacy , Nashik , Maharashtra , India
Abstract
Abstract
Aim
Oxidative stress due to chronic hyperglycaemia is a key factor in the development and progression of various microvascular complications including diabetic nephropathy (DN) and associated renal injury. Treatment with antioxidants is one of the strategies to protect the kidney from oxidative tissue damage to improve renal physiology during DN. The investigation, therefore, was designed to assess the nephroprotective effect of coenzyme Q10 (CoQ10) and N-acetylcysteine (NAC), either alone or in combination in streptozotocin (STZ)-nicotinamide (NAD) induced diabetic nephropathy (DN) in rats.
Methods
T2DM induced by STZ (55 mg/kg, i.p.)-NAD (110 mg/kg, i.p.) in Sprague-Dawley rats (220–250 g) was confirmed by the elevated blood glucose level and glycated haemoglobin. DN was assessed by renal function tests. The diabetic rats were treated with CoQ10 (10 mg/kg, p.o.) and/or NAC (300 mg/kg, p.o.) for 8 weeks after confirmation of DN. Oxidative tissue damage due to STZ-NAD was estimated by malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT), reduced glutathione (GSH), myeloperoxidase (MPO) and nitric oxide (NO) in the renal homogenate.
Results
Data showed significant alteration in serum and urinary creatinine, total protein, albumin, serum urea, blood urea nitrogen (BUN) and uric acid in diabetic animals as compared to the control rats. CoQ10 and/or NAC effectively alleviated the disturbances in renal function. Diabetic rats showed increased MDA, decreased SOD and CAT activities and decreased GSH along with a significant increase in MPO activity and nitrite content. Treatment with the aforementioned antioxidants and their combination ameliorated the kidney damage as indicated by the reduced OS with improved renal function.
Conclusion
The investigation suggests that the chronic hyperglycaemia-induced OS leads to the development and progression of DN. The combined treatment with CoQ10 and NAC has shown a remarkable nephroprotective effect suggesting that combined antioxidant therapy with CoQ10 and NAC may be useful in the attenuation of DN.
Subject
General Pharmacology, Toxicology and Pharmaceutics
Reference54 articles.
1. Agarwal N, Sadhukhan P. Therapeutic Insights against Oxidative Stress Induced Diabetic Nephropathy: A Review. J Autoimmune Disord. 2015; 1: 1–17.
2. Ahmad A, Mondello S, Di Paola R et al. Protective effect of apocynin, a NADPH-oxidase inhibitor, against contrast-induced nephropathy in the diabetic rats: A comparison with n-acetylcysteine. Eur J Pharmacol. 2012; 674: 397–406.
3. Ahmadi A, Mazooji N, Roozbeh J, Mazloom Z, Hasanzade J. Effect of alpha-lipoic acid and vitamin E supplementation on oxidative stress, inflammation, and malnutrition in hemodialysis patients. Iran J Kidney Dis. 2013; 7: 461–467.
4. Ahmadvand H. Effects of coenzyme Q10 on hemoglobin A1C, serum urea and creatinine in alloxan-induced Type 1 diabetic rats. Iran J Pharmacol Ther. 2012; 11: 64–67.
5. Alam M, Rahman M. Mitochondrial dysfunction in obesity: Potential benefit and mechanism of co-enzyme Q10 supplementation in metabolic syndrome. J Diabetes Metab Disord. 2014; 13: 1–11.