Therapeutic effect of valsartan against doxorubicin-induced renal toxicity in rats

Abstract

Objective(s): Doxorubicin (DXR)-induces glomerular atrophy and fibrosis in rat kidneys. The objective of the current study was to investigate the protective effects of valsartan on DXR-induced glomerular toxicity and its mechanisms of actions in rats. Materials and Methods: Male Sprague-Dawley (SD) rats were divided into four groups, and each group contains ten rats. First group was control and was treated with saline only. Treatment groups were injected with DXR (6.5 mg/kg) alone, or intragastric gavage with 10 mg/kg or 20 mg/kg of valsartan after DXR treatment.Results: Rats treated with DXR only showed significant changes in concentrations of urinary protein, serum creatinine (SCr), and blood urea nitrogen (BUN). Moreover, glomerular structural damages were observed in rats treated with DXR. Valsartan significantly alleviated the effect of DXR. Dramatic elevation in malondialdehyde (MDA), nitric oxide (NO), nitric oxide synthase (NOS) and significant reductions in the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) were seen after DXR treatment. These effects were effectively ameliorated by co-administration with valsartan. Conclusion: The findings of our study indicate that valsartan may play an important role in protecting DXR-induced renal toxicity, at least in part, through its antioxidant properties.

Keywords

• Antioxidants
• Doxorubicin
• Histopathology
• Nephrotoxicity
• Valsartan