D-pinitol attenuates cisplatin-induced nephrotoxicity in rats: Impact on pro-inflammatory cytokines.

ABSTRACT

Cisplatin has been widely used as a first-line agent against various forms of solid cancers. However, nephrotoxicity is the major limiting factor for its clinical use. Several clinical and pre-clinical studies have suggested different strategies for the reduction of cisplatin-induced nephrotoxicity. The present study was conducted to investigate the efficacy of D-Pinitol, against cisplatin-induced nephrotoxicity in Swiss albino mice. A single intraperitoneal injection of cisplatin (20 mg/kg) was used to induce nephrotoxicity in mice. Administration of cisplatin in mice is linked with elevated oxidative stress, imbalanced biochemical parameters, apoptosis and stimulation of mitogen-activated protein kinase (MAPK) pathway. D-Pinitol is a member of the flavonoid family and a chief constituent of Sutherlandia fruitesecnce. It was administered with saline water (10, 20, 40 mg/kg, p.o.) for seven consecutive days after a single dose of cisplatin. At the end of experiment, animals were sacrificed and biochemical parameters in serum and urine were recorded. Kidneys were isolated for the estimation of tumor necrosis factor-alpha, interleukin-1ß, interlukin-6 levels and histopathological evaluations. It was noted that D-Pinitol significantly ameliorated biochemical levels of serum and urinary creatinine and blood urea nitrogen. Tissue homogenate levels of TNF-α, IL-6, IL-1ß and the renal expression of tissue nitrites were also significantly decreased in D-Pinitol treated mice. These results were supplemented by histopathological findings. This study highlights the potential role of D-Pinitol against cisplatin-induced toxicity, exhibited through favorable alterations in biochemical and histological changes as well as reduction in oxidative stress and cytokine levels.