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肉碱泛酸钙联合治疗对丙戊酸诱导的肝毒性的潜在保护作用的证据。

Evidence for a potential protective effect of carnitine-pantothenic acid co-treatment on valproic acid-induced hepatotoxicity.

机构信息

University of California, Berkeley, Morgan Hall, Berkeley, CA 94720-3104, USA.

出版信息

Expert Rev Clin Pharmacol. 2014 Mar;7(2):211-8. doi: 10.1586/17512433.2014.871202. Epub 2014 Jan 22.

Abstract

Valproic acid is approved for treatment of seizures and manic episodes of bipolar disorder, and continues to be one of the most commonly prescribed antiepileptic drugs in the world. Hepatotoxicity is a rare but serious side effect resulting from its use, particularly in young patients. This adverse effect does not display normal dose-response curves and can be lethal in children. A review of the purported mechanisms of action suggest hepatotoxicity results from increased oxidative stress, caused by a reduction in beta-oxidation and an increase in activation of certain metabolizing enzymes. There is also evidence that both carnitine and pantothenic acid are involved in the regulation of valproic acid-induced hepatotoxic processes, and clinical evidence has shown that treatment with either compound shows protective effects against hepatotoxicity. These results suggest a potential increase in protective effects with cotreatment of carnitine and pantothenic acid.

摘要

丙戊酸被批准用于治疗癫痫发作和双相情感障碍的躁狂发作,并且仍然是世界上最常用的抗癫痫药物之一。其使用导致的肝毒性是一种罕见但严重的副作用,尤其是在年轻患者中。这种不良反应没有显示正常的剂量反应曲线,在儿童中可能是致命的。对所谓的作用机制的回顾表明,肝毒性是由β氧化减少和某些代谢酶的激活增加导致的氧化应激增加引起的。还有证据表明,肉碱和泛酸都参与了丙戊酸诱导的肝毒性过程的调节,临床证据表明,用这两种化合物治疗都显示出对肝毒性的保护作用。这些结果表明,与肉碱和泛酸联合治疗可能会增加保护作用。

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