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Toxicity of octanoate and decanoate in rat peripheral tissues: evidence of bioenergetic dysfunction and oxidative damage induction in liver and skeletal muscle

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Abstract

The accumulation of octanoic (OA) and decanoic (DA) acids in tissue is the common finding in medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD), the most frequent defect of fatty acid oxidation. Affected patients present hypoketotic hypoglycemia, rhabdomyolysis, hepatomegaly, seizures and lethargy, which may progress to coma and death. At present, the pathophysiological mechanisms underlying hepatic and skeletal muscle alterations in affected patients are poorly known. Therefore, in the present work, we investigated the in vitro effects of OA and DA, the accumulating metabolites in MCADD, on various bioenergetics and oxidative stress parameters. It was verified that OA and DA decreased complexes I–III, II–III and IV activities in liver and also inhibit complex IV activity in skeletal muscle. In addition, DA decreased complexes II–III activity in skeletal muscle. We also verified that OA and DA increased TBA-RS levels and carbonyl content in both tissues. Finally, DA, but not OA, significantly decreased GSH levels in rat skeletal muscle. Our present data show that the medium-chain fatty acids that accumulate in MCADD impair electron transfer through respiratory chain and elicit oxidative damage in rat liver and skeletal muscle. It may be therefore presumed that these mechanisms are involved in the pathophysiology of the hepatopathy and rhabdomyolysis presented by MCADD-affected patients.

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Acknowledgments

This work was supported by grants from CNPq, FAPESC and PIBIC/UNESC.

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Authors and Affiliations

  1. 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

    Giselli Scaini, Kellen R. Simon, Gustavo C. Ferreira, Emilio L. Streck & Patrícia F. Schuck

  2. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Anelise M. Tonin, Estela N. B. Busanello, Alana P. Moura & Moacir Wajner

  3. Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil

    Patrícia F. Schuck

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  1. Giselli Scaini
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Correspondence to Patrícia F. Schuck.

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Scaini, G., Simon, K.R., Tonin, A.M. et al. Toxicity of octanoate and decanoate in rat peripheral tissues: evidence of bioenergetic dysfunction and oxidative damage induction in liver and skeletal muscle. Mol Cell Biochem 361, 329–335 (2012). https://doi.org/10.1007/s11010-011-1119-4

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