Factor X, extracted from Pyropia yezoensis, prevent cisplatin-induced nephrotoxicity by down-regulating the MAPKs and NF-κB pathways

Abstract

Acute renal failure is a serious complication of the anticancer drug cisplatin. Cisplatin was known to exhibit cytotoxic effect to renal cells by induction poptosis through activation of p53, NF-κB and MAPK/p38 pathways. Thepotential role of Factor X, extracted from pyropia yezoensis, on cisplatininduced renal injury is unknown. Here, we assessed the effect of Factor X against cisplatin nephrotoxicity in human proximal tubular epithelial (HK2) cells. Factor X reduced cisplatin-induced cell death of HK2 cells. As well, Factor X concealed redox-sensitive transcription factor NF-κB activation via p65 nuclear translocation in HK2 cells. Factor X markedly attenuated cisplatin-induced p38/MAPK, ERK1/2, and JNK phosphorylation. Factor X also restored the renal antioxidants and increased the amount of total and nuclear accumulation of Nrf2 in HK2 cells. Moreover, Factor X inhibited cisplatin-induced apoptosis by Bax/Bcl2 imbalance. Firstly our findings suggest that Factor X ameliorates cisplatin-induced renal cell damage through up-regulation of antioxidant defense mechanisms and downregulation of the MAPKs and NF-κB signaling pathways. Thus, food and drug administration, may, in combination with cisplatin, represent a promising therapeutic strategy against cisplatin nephrotoxicity.