Safety and efficacy investigation of carnosine, an endogenous dipeptide against hypobaric hypoxia induced muscle protein loss

Abstract

Background

An urgent requirement necessitates maintenance of skeletal muscle health and physical performance during high altitude stress. Here, we deal with preclinical evaluation of a novel protective approach via supplementation of carnosine, an endogenous pleiotropic dipeptide. Protective efficacy of carnosine supplementation was investigated in hypobaric hypoxia (HH) exposed rat models. Further, safety study was also performed after prolonged oral administration of carnosine in rats.

Results

Oral supplementation with carnosine showed robust muscle protection at the dose of 50 mg/kg via increasing cross-sectional area (CSA) of myofibers. Co-supplementation of carnosine ameliorated HH induced muscle protein loss via decreasing calpain3, glucose regulating protein–78 (GRP-78) and myostatin activity and this was linked with increased Akt activity. Additionaly, carnosine also improved muscle strength via regulating energy metabolism (PGC-1α), myogenesis (Myo-G) and enhancing creatinine phosphokinase (CPK) activity. Further, safety efficacy of carnosine was also evaluated via administering different doses of carnosine for prolong period. The results suggested progressive increase in body weight, food intake, skeletal muscle weight and that was associated with enhance grip strength and myogenesis process. Interestingly, myostatin (a negative regulator of muscle mass) was declined in carnosine supplementated rats.

Conclusion

Carnosine showed no toxicity even when administered for long period. Ergo, mechanistic data depicted to ameliorate HH linked muscle protein loss at lower dose via influencing multiple deleterious pathways. Taken together, the results propose that endogenous pleiotropic dipeptide is a strong candidate for managing skeletal muscle health during high altitude stress condition.