Alis Rafael, Sanchis-Gomar Fabian, Risso-Ballester Jennifer, Perez-Quilis Carme, Cortell-Ballester Jose, Romagnoli Marco, Blesa Jose R, Emanuele Enzo
Research Institute "Dr. Viña Giner", Molecular and Mitochondrial Medicine, Catholic University of Valencia San Vicente Mártir, Valencia, Spain; School of Medicine, Catholic University of Valencia San Vicente Mártir, Valencia, Spain.
Research Institute "Dr. Viña Giner", Molecular and Mitochondrial Medicine, Catholic University of Valencia San Vicente Mártir, Valencia, Spain; Department of Physiology, University of Valencia, Valencia, Spain; Fundación Investigación Hospital Clínico Universitario/INCLIVA, Valencia, Spain.
Atherosclerosis. 2015 Mar;239(1):38-42. doi: 10.1016/j.atherosclerosis.2014.12.055. Epub 2014 Dec 31.
Although statins remain the cornerstone of lipid-lowering therapy for reducing the burden of atherosclerotic vascular disease, their administration has been associated with muscle-related adverse effects, including myalgia and rhabdomyolysis. Such adverse events are probably due to reduced antioxidant defenses associated with fewer intermediate metabolites in the cholesterol synthesis pathway. We hypothesize that the concomitant inhibition of xanthine oxidase via coadministration of allopurinol with statins could diminish reactive oxygen species (ROS)-related muscle damage, which would have in turn have positive effects on both the incidence of muscle-related adverse events and cardiovascular outcomes. Accordingly, inhibition of xanthine oxidase has been previously shown to be effective for reducing biomarkers of muscle damage following exercise in professional athletes. Because of the widespread statin utilization and increasing trends in their therapeutic use in atherosclerotic vascular diseases, the proposed strategy could have important clinical implications for reducing statin-induced myalgia and rhabdomyolysis.
尽管他汀类药物仍然是降低动脉粥样硬化性血管疾病负担的降脂治疗基石,但服用他汀类药物与肌肉相关的不良反应有关,包括肌痛和横纹肌溶解。此类不良事件可能是由于胆固醇合成途径中中间代谢物减少导致抗氧化防御能力降低所致。我们推测,通过将别嘌醇与他汀类药物联合使用来同时抑制黄嘌呤氧化酶,可能会减少活性氧(ROS)相关的肌肉损伤,这反过来又会对肌肉相关不良事件的发生率和心血管结局产生积极影响。因此,先前已证明抑制黄嘌呤氧化酶对于降低职业运动员运动后肌肉损伤的生物标志物有效。鉴于他汀类药物的广泛使用以及其在动脉粥样硬化性血管疾病治疗中的使用趋势不断增加,所提出的策略对于减少他汀类药物引起的肌痛和横纹肌溶解可能具有重要的临床意义。