MOLECULAR-BIOLOGICAL PROBLEMS OF DRUG DESIGN AND MECHANISM OF DRUG ACTION PROTECTIVE EFFECTS OF LIGANDROL AGAINST CISPLATIN-INDUCEDMOUSE MUSCLE CELL LINE TOXICITY

Cisplatin is an effective chemotherapeutic agent, but skeletal muscle dysfunction and fatigue are serious side effects after its administration. Ligandrol is a new nonsteroidal oral selective androgen receptor modulator used for muscle strengthening. The present study aimed to demonstrate the protective effects of ligandrol against cisplatin-induced muscle toxicity. 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 effects were determined by the egg chorioallantoic membrane method. Our results showed that combination treatment with cisplatin of ligandrol significantly (p < 0.05) increased cell viability, TAC levels, and caspase 3/7 gene expression, while significantly (p < 0.05) reducing TOS, LDH release, DNA fragmentation, lipid peroxidation, and intracellular calcium concentration levels compared to the cisplatin alone. Ligandrol significantly ameliorated cisplatin-induced irritant effects. This result suggested that ligandrol had a significant protective effect against cisplatin-induced muscle toxicity.