Abstract

Cisplatin is a potent widely-used chemotherapeutics; however, its clinical use is associated with nephrotoxicity. Renoprotective approaches are being discovered to halt the tubular cell death due to inflammatory and apoptotic burdens. In the present study, the renoprotective effects of different doses of biochanin A (10, 20 or 40?mg/kg) in mice treated with a single injection of cisplatin (10?mg/kg) were reported. Cisplatin administration resulted in marked increases in serum creatinine and blood urea nitrogen. Further, renal homogenates showed increased level of inflammatory cytokines and upregulation of the expression of p53 up-regulated modulator of apoptosis (PUMA), p53 and caspase 3 but downregulation in Nrf2 expression. Furthermore, cisplatin group showed marked necrosis and degenerated tubular lining epithelial cells with frequently detected apoptotic bodies. Mice treated with biochanin A (10, 20 or 40?mg/kg) for 14?days prior to cisplatin abrogated cisplatin-mediated damage. Furthermore, the elevated serum creatinine and urea levels were lessened by some doses of biochanin A, indicating protection against renal injury. Similarly, the changes in apoptosis and inflammatory markers have ameliorated to significant levels (P?<?0.05). The results suggest biochanin A as a nephroprotective agent against cisplatin toxicity. Overall, this nephroprotective effect of biochanin A involved anti-inflammatory and antiapoptotic activities.

Keywords

Acute kidney injury; Biochanin A; Cisplatin; Inflammation; p53 apoptosis; PUMA