Ribas Graziela S, Manfredini Vanusa, de Mari Jurema F, Wayhs Carlos Y, Vanzin Camila S, Biancini Giovana B, Sitta Angela, Deon Marion, Wajner Moacir, Vargas Carmen R
Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Ipiranga 2752, Porto Alegre, RS, 90610-000, Brazil.
Int J Dev Neurosci. 2010 Apr;28(2):127-32. doi: 10.1016/j.ijdevneu.2010.01.002. Epub 2010 Jan 25.
Disorders of propionate metabolism are autosomal recessive diseases clinically characterized by acute metabolic crises in the neonatal period and long-term neurological deficits whose pathophysiology is not completely established. There are increasing evidences demonstrating antioxidant properties for L-carnitine, which is used in the treatment of propionic and methylmalonic acidemias to increase the excretion of organic acids accumulated in tissues and biological fluids of the affected patients. In this work we aimed to evaluate lipid (malondialdehyde content) and protein (carbonyl formation and sulfhydryl oxidation) oxidative damage in plasma from patients with propionic and methylmalonic acidemias at the moment of diagnosis and during treatment with L-carnitine. We also correlated the parameters of oxidative damage with plasma total, free and esterified L-carnitine levels. We found a significant increase of malondialdehyde and carbonyl groups, as well as a reduction of sulfhydryl groups in plasma of these patients at diagnosis compared to controls. Furthermore, patients under treatment presented a marked reduction of the content of protein carbonyl groups, similar to controls, and malondialdehyde content in relation to patients at diagnosis. In addition, plasma total and free L-carnitine concentrations were negatively correlated with malondialdehyde levels. Taken together, the present data indicate that treatment significantly reduces oxidative damage in patients affected by disorders of propionate metabolism and that l-carnitine supplementation may be involved in this protection.
丙酸代谢紊乱是常染色体隐性疾病，临床特征为新生儿期急性代谢危机和长期神经功能缺损，其病理生理学尚未完全明确。越来越多的证据表明左旋肉碱具有抗氧化特性，左旋肉碱被用于治疗丙酸血症和甲基丙二酸血症，以增加患病患者组织和生物体液中积累的有机酸的排泄。在这项研究中，我们旨在评估丙酸血症和甲基丙二酸血症患者在诊断时以及左旋肉碱治疗期间血浆中的脂质（丙二醛含量）和蛋白质（羰基形成和巯基氧化）氧化损伤情况。我们还将氧化损伤参数与血浆总左旋肉碱、游离左旋肉碱和酯化左旋肉碱水平进行了关联分析。我们发现，与对照组相比，这些患者在诊断时血浆中的丙二醛和羰基显著增加，而巯基减少。此外，接受治疗的患者蛋白质羰基含量明显降低，与对照组相似，且丙二醛含量相对于诊断时的患者也有所降低。此外，血浆总左旋肉碱和游离左旋肉碱浓度与丙二醛水平呈负相关。综上所述，目前的数据表明治疗可显著降低受丙酸代谢紊乱影响患者的氧化损伤，且补充左旋肉碱可能参与了这种保护作用。
