Protective effects of ligandrol against cisplatin-induced muscle toxicity

Cisplatin is an important chemotherapeutic agent used in different cancer treatments. Cisplatin use also causes serious cytotoxic effects on muscle, nervous, kidney, and blood systems. Ligandrol is a new nonsteroidal oral selective androgen receptor modulator (SARM) developed for muscle strengthening. The present study aimed to demonstrate the protective effects of ligandrol against cisplatin-induced muscle toxicity. In the present study, cytotoxic effects were determined by cell viability (MTT) and lactate dehydrogenase (LDH) assays in mouse muscle cell lines (C2C12). The oxidant/antioxidant status was demonstrated by total antioxidant capacity (TAC) and total oxidative status (TOS). Cell cycle analysis, DNA fragmentation, caspase 3/7 activities, lipid peroxidation, and intracellular calcium concentration levels were evaluated. Irritant/antirritant effects were determined by the egg chorioallantoic membrane method (HET-CAM). Our results showed that combination treatment of cisplatin and ligandrol significantly (p<0,05) ameliorated the cell viability while significantly (p<0,05) reducing LDH release and intracellular calcium concentration which are signs of cell membrane damage. Ligandrol significantly (p <0,05) decreased cisplatin-induced TOS levels while significantly (p<0,05) increasing TAC levels. The increase in DNA fragmentation and the increase in malondialdehyde concentration, the end product of lipid peroxidation, induced by oxidative stress was inhibited. Combination administration of ligandrol and cisplatin activated apoptosis via increases in caspase 3/7 expression compared to cisplatin alone. The effectiveness of cisplatin, which showed strong irritant effects in the HET-CAM irritation trial, was significantly weakened after ligandrol applications. As a result, it was demonstrated for the first time with this study that ligandrol has a significant protective effect against cisplatin-induced muscle toxicity.