Protective effect of trans-sodium crocetinate on nephrotoxicity induced by cisplatin: in vitro and in vivo models.

Abstract

Trans-sodium crocetinate (TSC), a novel derivative of crocetin, has demonstrated potential protective effects against oxidative stress and apoptosis. This study aims to investigate the protective effect of TSC against cisplatin-induced nephrotoxicity by evaluating both in vivo and in vitro models. In the in vivo model, rats were pretreated with TSC (2.5, 5, and 10 mg/kg) for 5 days. Cisplatin (20 mg/kg) was injected on the 5th day to induce nephrotoxicity followed by TSC administration for an additional 2 days. Blood urea nitrogen (BUN) and serum creatinine (sCr) levels were measured to assess kidney function. Histopathological examinations and assessment of oxidative stress were conducted to evaluate renal tissue injury. In the in vitro model, HEK-293 cells were treated with cisplatin (150 µM) both with and without TSC pretreatment. Cell viability, reactive oxygen species (ROS) production, and apoptosis were subsequently evaluated. TSC significantly reduced BUN and sCr levels in rats exposed to cisplatin. Histopathological analysis revealed a reduction in tubular necrosis and other pathological changes associated with cisplatin toxicity. TSC also decreased MDA levels and increased GSH content in renal tissue. In HEK-293 cells, TSC pretreatment enhanced cell viability, reduced ROS production, and suppressed apoptosis by decreasing the Bax/Bcl-2 ratio and the expression of caspase-3 protein. TSC effectively protects against cisplatin-induced nephrotoxicity and cytotoxicity by reducing oxidative stress and apoptosis. These findings highlight TSC's potential as a therapeutic agent to mitigate the nephrotoxic effects of cisplatin in clinical settings.