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Oxidative Medicine and Cellular Longevity
Volume 2012, Article ID 856085, 9 pages
http://dx.doi.org/10.1155/2012/856085
Research Article

Combination Therapy with Losartan and Pioglitazone Additively Reduces Renal Oxidative and Nitrative Stress Induced by Chronic High Fat, Sucrose, and Sodium Intake

1Department of Pharmacology, Third-Grade Pharmacology Laboratory of State Administration of Traditional Chinese Medicine, Wannan Medical College, Anhui, Wuhu 241002, China
2Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
3Department of Gastroenterology, Yijishan Hospital Affiliated to Wannan Medical College, Anhui, Wuhu 241001, China
4Department of Nephrology, Yijishan Hospital Affiliated to Wannan Medical College, Anhui, Wuhu 241001, China

Received 15 August 2012; Revised 17 October 2012; Accepted 23 October 2012

Academic Editor: Guillermo Zalba

Copyright © 2012 Xiang Kong et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

We recently showed that combination therapy with losartan and pioglitazone provided synergistic effects compared with monotherapy in improving lesions of renal structure and function in Sprague-Dawley rats fed with a high-fat, high-sodium diet and 20% sucrose solution. This study was designed to explore the underlying mechanisms of additive renoprotection provided by combination therapy. Losartan, pioglitazone, and their combination were orally administered for 8 weeks. The increased level of renal malondialdehyde and expression of nicotinamide adenine dinucleotide phosphate oxidase subunit and nitrotyrosine as well as the decreased total superoxide dismutase activity and copper, zinc-superoxide dismutase expression were tangible evidence for the presence of oxidative and nitrative stress in the kidney of model rats. Treatment with both drugs, individually and in combination, improved these abnormal changes. Combination therapy showed synergistic effects in reducing malondialdehyde level, , and nitrotyrosine expression to almost the normal level compared with monotherapy. All these results suggest that the additive renoprotection provided by combination therapy might be attributed to a further reduction of oxidative and nitrative stress.