PMID- 24797612 OWN - NLM STAT- MEDLINE DCOM- 20140827 LR - 20161125 IS - 1879-0038 (Electronic) IS - 0378-1119 (Linking) VI - 545 IP - 1 DP - 2014 Jul 15 TI - Creatine prevents the imbalance of redox homeostasis caused by homocysteine in skeletal muscle of rats. PG - 72-9 LID - S0378-1119(14)00537-X [pii] LID - 10.1016/j.gene.2014.05.005 [doi] AB - Homocystinuria is a neurometabolic disease caused by severe deficiency of cystathionine beta-synthase activity, resulting in severe hyperhomocysteinemia. Affected patients present several symptoms including a variable degree of motor dysfunction, being that the pathomechanism is not fully understood. In the present study we investigated the effect of chronic hyperhomocysteinemia on some parameters of oxidative stress, namely 2'7'dichlorofluorescein (DCFH) oxidation, levels of thiobarbituric acid-reactive substances (TBARS), antioxidant enzyme activities (SOD, CAT and GPx), reduced glutathione (GSH), total sulfhydryl and carbonyl content, as well as nitrite levels in soleus skeletal muscle of young rats subjected to model of severe hyperhomocysteinemia. We also evaluated the effect of creatine on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injection of homocysteine (0.3-0.6 mumol/g body weight), and/or creatine (50mg/kg body weight) from their 6th to the 28th days age. Controls and treated rats were decapitated at 12h after the last injection. Chronic homocysteine administration increased 2'7'dichlorofluorescein (DCFH) oxidation, an index of production of reactive species and TBARS levels, an index of lipoperoxidation. Antioxidant enzyme activities, such as SOD and CAT were also increased, but GPx activity was not altered. The content of GSH, sulfhydril and carbonyl were decreased, as well as levels of nitrite. Creatine concurrent administration prevented some homocysteine effects probably by its antioxidant properties. Our data suggest that the oxidative insult elicited by chronic hyperhomocystenemia may provide insights into the mechanisms by which homocysteine exerts its effects on skeletal muscle function. Creatine prevents some alterations caused by homocysteine. CI - Copyright (c) 2014 Elsevier B.V. All rights reserved. FAU - Kolling, Janaina AU - Kolling J AD - Laboratorio de Neuroprotecao e Doencas Neurometabolicas, Departamento de Bioquimica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil; Laboratorio de Erros Inatos do Metabolismo, Departamento de Bioquimica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil. FAU - Scherer, Emilene B S AU - Scherer EB AD - Laboratorio de Neuroprotecao e Doencas Neurometabolicas, Departamento de Bioquimica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil; Laboratorio de Erros Inatos do Metabolismo, Departamento de Bioquimica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil. FAU - Siebert, Cassiana AU - Siebert C AD - Laboratorio de Neuroprotecao e Doencas Neurometabolicas, Departamento de Bioquimica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil; Laboratorio de Erros Inatos do Metabolismo, Departamento de Bioquimica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil. FAU - Marques, Eduardo Peil AU - Marques EP AD - Laboratorio de Neuroprotecao e Doencas Neurometabolicas, Departamento de Bioquimica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil; Laboratorio de Erros Inatos do Metabolismo, Departamento de Bioquimica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil. FAU - Dos Santos, Tiago Marcom AU - Dos Santos TM AD - Laboratorio de Neuroprotecao e Doencas Neurometabolicas, Departamento de Bioquimica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil; Laboratorio de Erros Inatos do Metabolismo, Departamento de Bioquimica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil. FAU - Wyse, Angela T S AU - Wyse AT AD - Laboratorio de Neuroprotecao e Doencas Neurometabolicas, Departamento de Bioquimica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil; Laboratorio de Erros Inatos do Metabolismo, Departamento de Bioquimica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil. Electronic address: wyse@ufrgs.br. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140502 PL - Netherlands TA - Gene JT - Gene JID - 7706761 RN - 0 (Fluoresceins) RN - 0 (Nitrites) RN - 0 (Thiobarbituric Acid Reactive Substances) RN - 0LVT1QZ0BA (Homocysteine) RN - 56NQM5UZT1 (2',7'-dichlorofluorescein) RN - EC 1.11.1.6 (Catalase) RN - EC 1.11.1.9 (Glutathione Peroxidase) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - GAN16C9B8O (Glutathione) RN - MU72812GK0 (Creatine) SB - IM MH - Animals MH - Catalase/metabolism MH - Creatine/metabolism/*pharmacology MH - Female MH - Fluoresceins/metabolism MH - Glutathione/metabolism MH - Glutathione Peroxidase/metabolism MH - Homeostasis/drug effects MH - Homocysteine/*pharmacology MH - Hyperhomocysteinemia/drug therapy/*metabolism MH - Male MH - Muscle, Skeletal/drug effects/*metabolism MH - Nitrites/metabolism MH - Oxidation-Reduction MH - Rats MH - Rats, Wistar MH - Superoxide Dismutase/metabolism MH - Thiobarbituric Acid Reactive Substances/metabolism OTO - NOTNLM OT - Creatine OT - Oxidative stress OT - Severe hyperhomocysteinemia OT - Soleus skeletal muscle EDAT- 2014/05/07 06:00 MHDA- 2014/08/29 06:00 CRDT- 2014/05/07 06:00 PHST- 2013/10/07 00:00 [received] PHST- 2014/03/14 00:00 [revised] PHST- 2014/05/01 00:00 [accepted] PHST- 2014/05/07 06:00 [entrez] PHST- 2014/05/07 06:00 [pubmed] PHST- 2014/08/29 06:00 [medline] AID - S0378-1119(14)00537-X [pii] AID - 10.1016/j.gene.2014.05.005 [doi] PST - ppublish SO - Gene. 2014 Jul 15;545(1):72-9. doi: 10.1016/j.gene.2014.05.005. Epub 2014 May 2.