WITHDRAWN: Protective effect of Emblica officinalis fruit extract on cisplatin-induced nephrotoxicity in female rats

Abstract

Cisplatin is one of the most common chemotherapeutic agent used in different solid tumors, but its main limiting factor is dose dependent nephrotoxicity. This study was designed to evaluate the protective role of Emblica officinalis against cisplatin induced nephrotoxicity in female rats. Emblica officinalis was orally administered for 10 days in 50, 100 and 200 mg/kg body weight. On day 7, 8 mg/kg of cisplatin was administered intra-peritoneally to rats in all groups. Serum creatinine, blood urea nitrogen and antioxidant levels were measured on day10. The renal damage was evaluated by histopathological, transmission electron microscopy and immunohistochemical analysis. We found that 200 mg/kg dose of Emblica officinalis significantly inhibited the elevation of biochemical parameters i.e. serum creatinine, blood urea nitrogen and oxidant stress marker (malondialdehyde) and increases the reduced levels of antioxidant markers (GSH and SOD). The immunohistochemical analysis reveals increased expression of various apoptotic and inflammatory biomarkers i.e. caspase-3, interleukin-1 (IL-1) and interleukin 6 (IL-6) in cisplatin group, which were significantly lowered by Emblica officinalis (200 mg/kg). Cisplatin treated rats have shown acute tubular necrosis and infiltration of inflammatory cells in rat kidney which was reversed after treatment with Emblica officinalis. Ultrastructural changes in renal tissues were studied by dysfunction in mitochondria and proximal tubule cells by transmission electron microscopy. In-silico studies revealed that ellagic acid is responsible for its nephroprotective effect. The above findings conclude that the Emblica officinalis may be used as add on therapy with cisplatin induced nephrotoxicity.