Beneficial effects of citrulline malate on skeletal muscle function in endotoxemic rat

Although citrulline malate (CM; CAS 54940-97-5, Stimol^®) is used against fatigue states, its anti-asthenic effect remains poorly documented. The objective of this double-blind study was to evaluate the effect of oral ingestion of CM on a rat model of asthenia, using in situ ³¹Phosphorus magnetic resonance spectroscopy (³¹P-MRS). Muscle weakness was induced by intraperitoneal injections of Klebsiella pneumoniae endotoxin (lipopolysaccharides at 3 mg/kg) at t₀ and t₀ + 24 h. For each animal, muscle function was investigated strictly non-invasively before (t₀ − 24 h) and during (t₀ + 48 h) endotoxemia, through a standardized rest-stimulation-recovery protocol. The transcutaneous electrical stimulation protocol consisted of 5.7 min of repeated isometric contractions at a frequency of 3.3 Hz, and force production was measured with an ergometer. CM supplementation in endotoxemic animals prevented the basal phosphocreatine/ATP ratio reduction and normalized the intracellular pH (pH_i) time-course during muscular activity as a sign of an effect at the muscle energetics level. In addition, CM treatment avoided the endotoxemia-induced decline in developed force. These results demonstrate the efficiency of CM for limiting skeletal muscle dysfunction in rats treated with bacterial endotoxin.