Molecular and Cellular Biochemistry

, Volume 366, Issue 1–2, pp 335–343 | Cite as

Phytanic acid disturbs mitochondrial homeostasis in heart of young rats: a possible pathomechanism of cardiomyopathy in Refsum disease

  • Mateus Grings
  • Anelise Miotti Tonin
  • Lisiane Aurélio Knebel
  • Ângela Zanatta
  • Alana Pimentel Moura
  • Carlos Severo Dutra Filho
  • Moacir Wajner
  • Guilhian Leipnitz


Phytanic acid (Phyt) accumulates in tissues and biological fluids of patients affected by Refsum disease. Although cardiomyopathy is an important clinical manifestation of this disorder, the mechanisms of heart damage are poorly known. In the present study, we investigated the in vitro effects of Phyt on important parameters of oxidative stress in heart of young rats. Phyt significantly increased thiobarbituric acid-reactive substances levels (P < 0.001) and carbonyl formation (P < 0.01), indicating that this fatty acid induces lipid and protein oxidative damage, respectively. In contrast, Phyt did not alter sulfhydryl oxidation. Phyt also decreased glutathione (GSH) concentrations (P < 0.05), an important non-enzymatic antioxidant defense. Moreover, Phyt increased 2′,7′-dichlorofluorescin oxidation (DCFH) (P < 0.01), reflecting increased reactive species generation. We also found that the induced lipid and protein oxidative damage, as well as the decreased GSH levels and increased DCFH oxidation provoked by this fatty acid were prevented or attenuated by the reactive oxygen species scavengers melatonin, trolox, and GSH, but not by the nitric oxide inhibitor n ω-nitro-l-arginine methyl ester, suggesting that reactive oxygen species were involved in these effects. Next, we verified that Phyt strongly inhibited NADH-cytochrome c oxidoreductase (complex I–III) activity (P < 0.001) in heart supernatants, and decreased membrane potential and the NAD(P)H pool in heart mitochondria, indicating that Phyt acts as a metabolic inhibitor and as an uncoupler of the electron transport chain. Therefore, it can be presumed that disturbance of cellular energy and redox homeostasis induced by Phyt may possibly contribute to the cardiomyopathy found in patients affected by Refsum disease.


Refsum disease Phytanic acid Oxidative stress Heart 



This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Programa de Apoio a Núcleos de Excelência (PRONEX II), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Pró-reitoria de Pesquisa/Universidade Federal do Rio Grande do Sul (PROPESQ/UFRGS), Financiadora de estudos e projetos (FINEP), Rede Instituto Brasileiro de Neurociência (IBN-Net) # 01.06.0842-00 and Instituto Nacional de Ciência e Tecnologia em Excitotoxicidade e Neuroproteção (INCT-EN).


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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Mateus Grings
    • 1
  • Anelise Miotti Tonin
    • 1
  • Lisiane Aurélio Knebel
    • 1
  • Ângela Zanatta
    • 1
  • Alana Pimentel Moura
    • 1
  • Carlos Severo Dutra Filho
    • 1
  • Moacir Wajner
    • 1
    • 2
  • Guilhian Leipnitz
    • 1
  1. 1.Departamento de Bioquímica, Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Serviço de Genética MédicaHospital de Clínicas de Porto AlegrePorto AlegreBrazil

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