Carboxymethylated Poria cocos Polysaccharides Mitigate Cisplatin‐Induced Hepatorenal Injury by Activating the PLC‐PKC‐Nrf2 Signaling Pathway

Abstract

ABSTRACT Cisplatin, a commonly used chemotherapy drug, inevitably causes damage to the liver and kidneys while exerting its anti‐tumor effects. Carboxymethylated Poria cocos polysaccharides (CMP) have anti‐inflammatory, antioxidant, and organ‐protective properties, and also exhibit significant anti‐tumor activity. Therefore, this study aims to investigate the effects of CMP on cisplatin‐induced hepatorenal damage in mice. The results showed that CMP treatment significantly mitigated abnormalities in hepatorenal function indicators and tissue damage induced by cisplatin. Furthermore, CMP significantly suppressed the increase in levels of inflammatory factors in peripheral and hepatorenal tissues, as well as the infiltration of immune cells induced by cisplatin. Additionally, CMP significantly enhanced the antioxidant capacity of hepatorenal tissues and inhibited oxidative damage caused by cisplatin. In vitro, CMP have also been shown to protect renal tubular epithelial cells and hepatocytes from cisplatin‐induced damage. Mechanistically, our studies indicated that CMP activate Nrf2 through a phosphorylation pathway that is independent of Keap1 and reliant on PLC‐PKC signaling. In conclusion, our findings suggest that CMP has the potential to serve as an adjunctive agent in cisplatin chemotherapy to protect the kidneys and liver from damage.