title: Homocysteine induces energy imbalance in rat skeletal muscle: is creatine a protector?
abstract: Homocystinuria is a neurometabolic disease caused by a severe deficiency of cystathionine beta-synthase activity, resulting in severe hyperhomocysteinemia. Affected patients present several symptoms including a variable degree of motor dysfunction. In this study, we investigated the effect of chronic hyperhomocysteinemia on the cell viability of the mitochondrion, as well as on some parameters of energy metabolism, such as glucose oxidation and activities of pyruvate kinase, citrate synthase, isocitrate dehydrogenase, malate dehydrogenase, respiratory chain complexes and creatine kinase in gastrocnemius rat skeletal muscle. We also evaluated the effect of creatine on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injections of homocysteine (0.3-0.6 µmol/g body weight) and/or creatine (50 mg/kg body weight) from the 6th to the 28th days of age. The animals were decapitated 12 h after the last injection. Homocysteine decreased the cell viability of the mitochondrion and the activities of pyruvate kinase and creatine kinase. Succinate dehydrogenase was increased other evaluated parameters were not changed by this amino acid. Creatine, when combined with homocysteine, prevented or caused a synergistic effect on some changes provoked by this amino acid. Creatine per se or creatine plus homocysteine altered glucose oxidation. These findings provide insights into the mechanisms by which homocysteine exerts its effects on skeletal muscle function, more studies are needed to elucidate them. Although creatine prevents some alterations caused by homocysteine, it should be used with caution, mainly in healthy individuals because it could change the homeostasis of normal physiological functions.
authors.affiliation: Laboratório de Neuroproteção e Doenças Neurometabólicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Laboratório de Erros Inatos do Metabolismo, Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Janaína
authors.initials: J
authors.lastname: Kolling
authors.forename: Emilene B S
authors.initials: EB
authors.lastname: Scherer
authors.forename: Cassiana
authors.initials: C
authors.lastname: Siebert
authors.forename: Fernanda
authors.initials: F
authors.lastname: Hansen
authors.forename: Felipe V
authors.initials: FV
authors.lastname: Torres
authors.forename: Giselli
authors.initials: G
authors.lastname: Scaini
authors.forename: Gabriela
authors.initials: G
authors.lastname: Ferreira
authors.forename: Rodrigo B
authors.initials: RB
authors.lastname: de Andrade
authors.forename: Carlos A S
authors.initials: CA
authors.lastname: Gonçalves
authors.forename: Emílio L
authors.initials: EL
authors.lastname: Streck
authors.forename: Clovis M D
authors.initials: CM
authors.lastname: Wannmacher
authors.forename: Angela T S
authors.initials: AT
authors.lastname: Wyse
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002952:Citric Acid Cycle; D003401:Creatine / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D004734:Energy Metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism* / Q000494:pharmacology; D020138:Hyperhomocysteinemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
chemical_list: D006710:Homocysteine; D005947:Glucose; D003401:Creatine