Hindawi Publishing Corporation International Journal of Cell Biology Volume 2011, Article ID 390238, 9 pages doi:10.1155/2011/390238 Research Article Doxorubicin Induced Nephrotoxicity: Protective Effect of Nicotinamide Sule Ayla, 1 Ismail Seckin, 2 Gamze Tanriverdi, 2 Mujgan Cengiz, 3 Mediha Eser, 3 B. C. Soner, 4 and Gulperi Oktem 5 1 Suleymaniye Woman Health Hospital, 34122 Istanbul, Turkey 2 Department of Histology and Embryology, Cerrahpasa School of Medicine, Istanbul University, 34452 Istanbul, Turkey 3 Department of Medical Biology, Cerrahpasa School of Medicine, Istanbul University, 34452 Istanbul, Turkey 4 Department of Pharmacology, Meram School of Medicine, Selcuk University, 42080 Konya, Turkey 5 Department of Histology and Embryology, Ege University School of Medicine, 35100 Izmir, Turkey Correspondence should be addressed to Gulperi Oktem, gulperi.oktem@ege.edu.tr Received 31 January 2011; Revised 25 April 2011; Accepted 16 May 2011 Academic Editor: Richard Gomer Copyright © 2011 Sule Ayla 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. Introduction. Nephrotoxicity is one of the important side effects of anthracycline antibiotics. The aim of this study was to investigate the effects of nicotinamide (NAD), an antioxidant agent, against nephrotoxicity induced by doxorubicin (DXR). Methods. The rats were divided into control, NAD alone, doxorubicin (20 mg/kg, i.p.) and DXR plus NAD (200 mg/kg, i.p.) groups. At the end of the 10th day, kidney tissues were removed for light microscopy and analysis. The level of tissues’ catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), inducible nitric oxide (iNOS) and endothelial nitric oxide (eNOS) activities were determined. Results. The activities of CAT, GPx, and GSH were decreased, and Po was increased in renal tissue of doxorubicin group compared with other groups. The tissue of the doxorubicin group showed some histopathological changes such as glomerular vacuolization and degeneration, adhesion to Bowman’s capsule and thickening and untidiness of tubular and glomerular capillary basement membranes. Histopathological examination showed that NAD prevented partly DXR-induced tubular and glomerular damage. Conclusions. Pretreatment with NAD protected renal tissues against DXR-induced nephrotoxicity. Preventive effects of NAD on these renal lesions may be via its antioxidant and anti-inflammatory action. 1. Introduction Quinine-containing anthracycline antibiotic doxorubicin (DXR) has been used for the treatment of cancer since 1969. In spite of its high antitumor efficacy, DXR’s use in chemotherapy has been largely limited due to its cardiac, renal, pulmonary, testicular, and hematological toxicities [1, 2]. DXR causes an imbalance between free oxygen radicals and antioxidants. The disturbance in oxidant-antioxidant systems which has been demonstrated with lipid peroxida- tion (LPO) and protein oxidation results with tissue injury [3]. Although the exact mechanism of DXR-induced nephro- toxicity remains unknown, it is believed that the toxicity may be mediated through free radical formation, iron-dependent oxidative damage of biological macromolecules, membrane LPO, and protein oxidation [4]. DXR-induced changes in the kidneys of rats include increased glomerular capillary permeability and tubular atrophy [5]. Nitric oxide (NO) is a free radical gas which acts as a cytoprotective or a cytotoxic agent. NO is generated by either endothelial nitric oxide synthase (eNOS) or inducible nitric oxide synthase (iNOS) [6]. Possible role of DXR in NOS metabolism occurs via direct or indirect stimulation of NO production, and this might be a consequence of increased free radical generation. Free radical production and/or NO release induced by DXR is entirely responsible for the DXR-induced toxicity [7]. Mitochondria has been defined as one of the targets in DXR-induced subcellular damage in the tissue. In addition, it has been shown that DXR could stimulate transmembranal arginine transport to provide increased substrate and activate NOS mediated NO- production [8].