Evaluation of hepatic health, muscle strength and antioxidant response for therapeutic insight of ostarine in mice

Selective androgen receptor modulators (SARMs) are a family of small molecules that bind to androgen receptors to elicit therapeutic responses in age-related disorders. SARMs exert their beneficial effects by preventing muscle wasting and supporting bone regeneration, as well as helping in overcoming sarcopenia. Ostarine, a known SARM, improves muscle strength and helps in reversing osteoporosis. Preliminary studies have affirmed ostarine to be toxic at higher doses; however, extensive analysis remains to be done. We have undertaken this study for the first time to understand whether ostarine at higher dosage may cause adverse effects on mice liver. The cellular antioxidant framework, liver marker enzymes and histoarchitectural changes of hepatic tissue were investigated. Further, Rotarod and actophotometer tests were undertaken as markers, and mice treated with ostarine displayed increased muscular strength and locomotor activity. However, activities of liver marker enzymes namely, serum glutamic pyruvic transaminase and alkaline phosphatase, were significantly elevated in mice treated with ostarine. Further, ostarine treatment caused a significant increase in the levels of reactive oxygen species, lipid peroxidation and protein carbonyl content but revealed an appreciable decrease in glutathione levels. The activities of antioxidative enzymes were also significantly elevated following ostarine treatment. Further, ostarine treatment resulted in mitochondrial swelling and caused alterations in normal hepatic histoarchitecture. Therefore, the present study clearly indicates that ostarine may be an effective drug against locomotive disorders, but is toxic to the liver at higher dose.