title: Beneficial effects of citrulline malate on skeletal muscle function in endotoxemic rat.
abstract: 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 (31)Phosphorus magnetic resonance spectroscopy ((31)P-MRS). Muscle weakness was induced by intraperitoneal injections of Klebsiella pneumoniae endotoxin (lipopolysaccharides at 3 mg/kg) at t(0) and t(0)+24 h. For each animal, muscle function was investigated strictly non-invasively before (t(0)-24 h) and during (t(0)+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.
authors.affiliation: Centre de Résonance Magnétique Biologique et Médicale, UMR CNRS 6612, Faculté de Médecine de Marseille, Université de Méditerranée, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 5, France. benoit.giannesini@univmed.fr
authors.forename: Benoît
authors.initials: B
authors.lastname: Giannesini
authors.forename: Marguerite
authors.initials: M
authors.lastname: Izquierdo
authors.forename: Yann
authors.initials: Y
authors.lastname: Le Fur
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Cozzone
authors.forename: Marc
authors.initials: M
authors.lastname: Verleye
authors.forename: Marie-Emmanuelle
authors.initials: ME
authors.lastname: Le Guern
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Gillardin
authors.forename: David
authors.initials: D
authors.lastname: Bendahan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002956:Citrulline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004311:Double-Blind Method; D019446:Endotoxemia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D004731:Endotoxins / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007711:Klebsiella pneumoniae / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008293:Malates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D005082:Physical Exertion / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D004731:Endotoxins; D008293:Malates; D002956:Citrulline; C071162:citrulline malate