BACKGROUND The mitochondrial fatty acids oxidation disorders (FAOD) are inherited metabolic disorders (IMD) characterized by the accumulation of fatty acids of different sizes of chain according to the affected enzyme. METHODS This study evaluated the lipid peroxidation by the measurement of 8-isoprostanes, nitrosative stress parameters by the measurement of nitrite and nitrate content and DNA and RNA oxidative damage by the measurement of oxidized guanine species in urine samples from long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD), medium-chain acyl-CoA dehydrogenase deficiency (MCADD) and multiple acyl-CoA dehydrogenase deficiency (MADD) patients. Also, we analyzed the in vitro DNA damage by comet assay induced by adipic acid, suberic acid, hexanoylglycine and suberylglycine, separated and in combination, as well as the effect of l-carnitine in human leukocytes. RESULTS An increase on 8-isoprostanes levels in all groups of patients was observed. The nitrite and nitrate levels were increased in LCHADD patients. DNA and RNA damage evaluation revealed increase on oxidized guanine species levels in LCHADD and MADD patients. The in vitro evaluation revealed an increase on the DNA damage induced by all metabolites, besides a potencialyzed effect. l-carnitine decreased the DNA damage induced by the metabolites. CONCLUSION These results demonstrate that toxic metabolites accumulated could be related to the increased oxidative and nitrosative stress of FAOD patients and that the metabolites, separated and in combination, cause DNA damage, which was reduced by l-carnitine, demonstrating antioxidant protection. GENERAL SIGNIFICANCE This work demonstrated oxidative stress in FAOD patients and the genotoxic potential of MCADD metabolites and the protective effect of l-carnitine.

中文翻译：

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线粒体脂肪酸氧化失调患者的氧化损伤以及左旋肉碱对累积代谢产物诱导的DNA损伤的体外作用。

背景技术线粒体脂肪酸氧化失调（FAOD）是遗传性代谢失调（IMD），其特征是根据受影响的酶，不同链大小的脂肪酸的积累。方法本研究通过测定8个异戊烷的脂质过氧化，通过测定亚硝酸盐和硝酸盐含量的亚硝化应激参数以及通过测量长链3-羟酰基-尿液中氧化鸟嘌呤种类的DNA和RNA氧化损伤来评估脂质过氧化反应。 CoA脱氢酶缺乏症（LCHADD），中链酰基CoA脱氢酶缺乏症（MCADD）和多酰基CoA脱氢酶缺乏症（MADD）患者。另外，我们还通过彗星试验分析了己二酸，辛二酸，己酰甘氨酸和辛二酰甘氨酸分别分离和组合诱导的体外DNA损伤，以及左旋肉碱在人白细胞中的作用。结果观察到所有患者组中8-异前列腺素水平均升高。LCHADD患者的亚硝酸盐和硝酸盐水平升高。DNA和RNA损伤评估显示LCHADD和MADD患者的氧化鸟嘌呤种类水平增加。体外评估显示，除了增强电位作用外，所有代谢物诱导的DNA损伤都有所增加。左旋肉碱减少了由代谢产物引起的DNA损伤。结论这些结果表明，积累的有毒代谢物可能与FAOD患者的氧化和亚硝化应激增加有关，并且这些代谢物分离并结合在一起会引起DNA损伤，其被左旋肉碱减少，表明了抗氧化保护作用。