Yıldızhan Kenan, Huyut Zübeyir, Altındağ Fikret
Department of Biophysics, Faculty of Medicine, Van Yuzuncu Yil University, TR-65090, Van, Turkey.
Department of Biochemistry, Faculty of Medicine, Van Yuzuncu Yil University, Van, Turkey.
Biol Trace Elem Res. 2023 May;201(5):2458-2469. doi: 10.1007/s12011-022-03377-2. Epub 2022 Aug 4.
Doxorubicin (DOXR) is an important chemotherapeutic drug used in cancer treatment for many years. Several studies reported that the use of DOXR increased toxicity by causing an increase in oxidative stress (OS), especially in the heart. In this study, we investigated the protective effect of selenium (Se) and the role of transient receptor potential melastatin-2 (TRPM2) channel activation by using N-(p-amylcinnamoyl) anthranilic acid (ACA) in a model of DOXR-induced cardiotoxicity. Sixty female rats were equally divided into the control, dimethyl sulfoxide (DMSO), DOXR, DOXR + Se, DOXR + ACA, and DOXR + Se + ACA groups. Glutathione (GSH), glutathione peroxidase (GSH-Px), caspases (Cas) 3 and 9, interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS), poly [ADP-ribose] polymerase 1 (PARP-1), and TRPM2 channel levels were measured by ELISA. In addition, histopathological examination was performed in cardiac tissues and TNF-α, caspase 3, and TRPM2 channel expression levels were determined immunohistochemically. The levels of GSH, GSH-Px, caspases 3 and 9, IL-1β, TNF-α, ROS, PARP-1, and TRPM2 channel in serum, and cardiac tissue in the DOXR group were higher than in the control and DMSO groups (p < 0.05). However, these parameters in Se and/or ACA treatment groups were lower than in the DOXR group (p < 0.05). Also, we determined that Se and/or ACA treatment together with DOXR application decreased the TNF-α, Cas-3, and TRPM2 channel expression levels in the cardiac tissue. The data showed that administration of Se and/or ACA treatment together with DOXR may be used as a therapeutic agent in preventing DOXR-induced cardiotoxicity.
阿霉素(DOXR)是一种多年来用于癌症治疗的重要化疗药物。多项研究报告称,使用DOXR会因氧化应激(OS)增加而导致毒性增加,尤其是在心脏中。在本研究中,我们通过使用N-(对戊基肉桂酰基)邻氨基苯甲酸(ACA),在DOXR诱导的心脏毒性模型中研究了硒(Se)的保护作用以及瞬时受体电位褪黑素2(TRPM2)通道激活的作用。将60只雌性大鼠平均分为对照组、二甲基亚砜(DMSO)组、DOXR组、DOXR + Se组、DOXR + ACA组和DOXR + Se + ACA组。通过酶联免疫吸附测定法(ELISA)测量谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-Px)、半胱天冬酶(Cas)3和9、白细胞介素1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、活性氧(ROS)、聚[ADP-核糖]聚合酶1(PARP-1)和TRPM2通道水平。此外,对心脏组织进行组织病理学检查,并通过免疫组织化学法测定TNF-α、半胱天冬酶3和TRPM2通道的表达水平。DOXR组血清和心脏组织中的GSH、GSH-Px、半胱天冬酶3和9、IL-1β、TNF-α、ROS、PARP-1和TRPM2通道水平高于对照组和DMSO组(p < 0.05)。然而,硒和/或ACA治疗组的这些参数低于DOXR组(p < 0.05)。此外,我们确定,DOXR应用联合硒和/或ACA治疗可降低心脏组织中TNF-α、Cas-3和TRPM2通道的表达水平。数据表明,DOXR联合硒和/或ACA治疗可作为预防DOXR诱导的心脏毒性的治疗剂。