title: Acute renal failure potentiates brain energy dysfunction elicited by methylmalonic acid.
abstract: The influence of acute renal failure induced by gentamicin administration on the effects of MMA on mitochondrial respiratory chain complexes, citrate synthase, succinate dehydrogenase and creatine kinase activities in cerebral cortex and kidney of young rats were investigated. Animals received one intraperitoneal injection of saline or gentamicin (70 mg/kg). One hour after, the animals received three consecutive subcutaneous injections of MMA (1.67 μmol/g) or saline (11 h interval between injections) and 60 min after the last injection the animals were killed. Acute MMA administration decreased creatine kinase activity in both tissues and increased complexes I-III activity in cerebral cortex. Creatine kinase activity was also inhibited by gentamicin administration. Simultaneous administration of MMA and gentamicin increased the activities of citrate synthase in cerebral cortex and kidney and complexes II-III in cerebral cortex. The other enzyme activities in cerebral cortex and kidney of animals receiving MMA plus gentamicin did not significantly differ from those observed in animals receiving only MMA. Our present data is line with the hypothesis that MMA acts as a toxin in brain and kidney of rats and suggest that renal injury potentiates the toxicity of MMA on the Krebs cycle and respiratory chain in brain and peripheral tissues.
authors: Laboratório de Erros Inatos do Metabolismo, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors: Patrícia F
authors: PF
authors: Schuck
authors: Silvana B
authors: SB
authors: Januário
authors: Kellen R
authors: KR
authors: Simon
authors: Giselli
authors: G
authors: Scaini
authors: Renato L
authors: RL
authors: Mafioleti
authors: Fernanda
authors: F
authors: Malgarin
authors: Leticia F
authors: LF
authors: Pettenuzzo
authors: Emilio L
authors: EL
authors: Streck
authors: Gustavo C
authors: GC
authors: Ferreira
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000150:complications*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001928:Brain Diseases, Metabolic / Q000139:chemically induced* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004734:Energy Metabolism / Q000187:drug effects*; D008297:Male; D008764:Methylmalonic Acid / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008764:Methylmalonic Acid