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 peroxidation (LPO) and protein oxidation results with tissue injury [3]. Although the exact mechanism of DXR-induced nephrotoxicity 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
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