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<p>Methylmalonic acidemia and propionic acidemia are inborn errors of metabolism caused by genetic mutations in mitochondrial enzymes involved in propionate metabolism. When these enzymes fail to function properly, organic acids accumulate in tissues and biological fluids. The brain is the primary tissue affected in these disorders, particularly due to the accumulation of organic acids. Oxidative stress and DNA damage play an important role in the pathophysiology of these diseases and may contribute to neurological impairment. In this context, the present study aimed to evaluate the in vitro effects of L-carnitine, N-acetylcysteine, and coenzyme Q10 on DNA damage induced by metabolites accumulated in methylmalonic and propionic acidemias. Leukocytes isolated from whole blood were used, and DNA damage was assessed using the comet assay. Our results demonstrated that metabolites accumulated in these disorders were responsible for inducing DNA damage, individually and in combination. In addition, all tested antioxidants exhibited protective effects against DNA damage. This study is the first to demonstrate the genotoxic effects of other metabolites beyond methylmalonic and propionic acids and to show the protective potential effect of different antioxidants in mitigate DNA damage. Taken together, these findings reinforce the need for clinical trials evaluating antioxidant-based therapies to improve prognosis and clinical outcomes in patients with methylmalonic acidemia and propionic acidemia.</p>

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Protective in vitro effects of antioxidants against DNA damage induced by metabolites accumulated in propionic and methylmalonic acidemias

  • 期刊论文

  • 发表日期：

    2026年6月30日

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  • Bianca Gomes dos Reis,
  • Franciele Fátima Lopes,
  • Luísa Maria Bosquetti Tedesco,
  • Silvia Muller de Moura Sarmento,
  • Vanusa Manfredini,
  • Carmen Regla Vargas

摘要

Methylmalonic acidemia and propionic acidemia are inborn errors of metabolism caused by genetic mutations in mitochondrial enzymes involved in propionate metabolism. When these enzymes fail to function properly, organic acids accumulate in tissues and biological fluids. The brain is the primary tissue affected in these disorders, particularly due to the accumulation of organic acids. Oxidative stress and DNA damage play an important role in the pathophysiology of these diseases and may contribute to neurological impairment. In this context, the present study aimed to evaluate the in vitro effects of L-carnitine, N-acetylcysteine, and coenzyme Q10 on DNA damage induced by metabolites accumulated in methylmalonic and propionic acidemias. Leukocytes isolated from whole blood were used, and DNA damage was assessed using the comet assay. Our results demonstrated that metabolites accumulated in these disorders were responsible for inducing DNA damage, individually and in combination. In addition, all tested antioxidants exhibited protective effects against DNA damage. This study is the first to demonstrate the genotoxic effects of other metabolites beyond methylmalonic and propionic acids and to show the protective potential effect of different antioxidants in mitigate DNA damage. Taken together, these findings reinforce the need for clinical trials evaluating antioxidant-based therapies to improve prognosis and clinical outcomes in patients with methylmalonic acidemia and propionic acidemia.