title: Acute renal failure potentiates methylmalonate-induced oxidative stress in brain and kidney of rats.
abstract: Tissue methylmalonic acid (MMA) accumulation is the biochemical hallmark of methylmalonic acidemia. The disease is clinically characterized by progressive neurological deterioration and kidney failure, whose pathophysiology is still unclear. In the present work we investigated the effects of acute MMA administration on various parameters of oxidative stress in cerebral cortex and kidney of young rats, as well as the influence of acute renal failure on MMA-elicited effects on these parameters. Acute renal failure was induced by gentamicin, an aminoglycoside antibiotic whose utilization over prolonged periods causes nephrotoxicity. The administration of gentamicin alone increased carbonyl content and inhibited superoxide dismutase (SOD) activity in cerebral cortex, as well as increased thiobarbituric acid-reactive substances (TBA-RS) and sulfhydryl levels and diminished glutathione peroxidase activity in kidney. On the other hand, MMA administration increased TBA-RS levels in cerebral cortex and decreased SOD activity in kidney. Furthermore, the simultaneous administration of MMA and gentamicin to the rats provoked an augment in TBA-RS levels and superoxide generation in cerebral cortex and in TBA-RS, carbonyl and sulfhydryl levels in kidney, while diminished SOD activity in both studied tissues. Finally, nitrate/nitrite content, reduced glutathione levels, 2',7'-dihydrodichlorofluorescein oxidation and catalase activity were not affected by this animal treatment in either tissue. In conclusion, our present data are in 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 oxidative stress parameters in brain and peripheral tissues.
authors.affiliation: Laboratório de Erros Inatos do Metabolismo, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma , SC , Brazil. patricia.schuck@pq.cnpq.br
authors.forename: P F
authors.initials: PF
authors.lastname: Schuck
authors.forename: L
authors.initials: L
authors.lastname: Alves
authors.forename: L F
authors.initials: LF
authors.lastname: Pettenuzzo
authors.forename: F
authors.initials: F
authors.lastname: Felisberto
authors.forename: L B
authors.initials: LB
authors.lastname: Rodrigues
authors.forename: B W
authors.initials: BW
authors.lastname: Freitas
authors.forename: F
authors.initials: F
authors.lastname: Petronilho
authors.forename: F
authors.initials: F
authors.lastname: Dal-Pizzol
authors.forename: E L
authors.initials: EL
authors.lastname: Streck
authors.forename: G C
authors.initials: GC
authors.lastname: Ferreira
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism*; D000592:Amino Acid Metabolism, Inborn Errors / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D002374:Catalase / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D003404:Creatinine / Q000097:blood; D005839:Gentamicins; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008764:Methylmalonic Acid; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D050050:Protein Carbonylation; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D005839:Gentamicins; D009566:Nitrates; D009573:Nitrites; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D008764:Methylmalonic Acid; D003404:Creatinine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione