Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-USP, Ribeirão Preto, SP, Brasil.
J Toxicol Environ Health A. 2012;75(16-17):981-90. doi: 10.1080/15287394.2012.696512.
Cisplatin is a highly effective chemotherapeutic drug; however, its use is limited by nephrotoxicity. Studies showed that the renal injury produced by cisplatin involves oxidative stress and cell death mediated by apoptosis and necrosis in proximal tubular cells. The use of antioxidants to decrease cisplatin-induced renal cell death was suggested as a potential therapeutic measure. In this study the possible protective effects of carvedilol, a beta blocker with antioxidant activity, was examined against cisplatin-induced apoptosis in HK-2 human kidney proximal tubular cells. The mitochondrial events involved in this protection were also investigated. Four groups were used: controls (C), cisplatin alone at 25 μM (CIS), cisplatin 25 μM plus carvedilol 50 μM (CV + CIS), and carvedilol alone 50 μM (CV). Cell viability, apoptosis, caspase-9, and caspase-3 were determined. Data demonstrated that carvedilol effectively increased cell viability and minimized caspase activation and apoptosis in HK-2 cells, indicating this may be a promising drug to reduce nephrotoxicity induced by cisplatin.
顺铂是一种高效的化疗药物;然而,其应用受到肾毒性的限制。研究表明,顺铂引起的肾损伤涉及氧化应激和细胞凋亡和坏死介导的近端肾小管细胞死亡。使用抗氧化剂来减少顺铂诱导的肾细胞死亡被认为是一种潜在的治疗措施。在这项研究中,检查了具有抗氧化活性的β受体阻滞剂卡维地洛对人肾近端肾小管细胞 HK-2 顺铂诱导的细胞凋亡的可能保护作用。还研究了这种保护中涉及的线粒体事件。使用了四组:对照组(C)、单独顺铂 25 μM(CIS)、顺铂 25 μM 加卡维地洛 50 μM(CV+CIS)和单独卡维地洛 50 μM(CV)。测定细胞活力、细胞凋亡、半胱天冬酶-9 和半胱天冬酶-3。数据表明,卡维地洛能有效增加细胞活力,最大限度地减少 HK-2 细胞中 caspase 的激活和凋亡,表明这可能是一种减少顺铂引起的肾毒性的有前途的药物。