Department of Embryology and Histology, Faculty of Medicine, Inonu University, 44280 Malatya, Turkey.
J Chem Neuroanat. 2012 Jan;43(1):43-7. doi: 10.1016/j.jchemneu.2011.09.003. Epub 2011 Sep 16.
Several studies have well confirmed the contribution of oxidative stress in the pathogenesis of methotrexate (MTX)-induced damage in the various organs. Many agents have been tested experimentally to reduce or inhibit the oxidative stress. The aim of this study was to determine the possible protective effect of chlorogenic acid (CLG) on MTX-induced cerebellar damage in rats. The rats were randomly divided into three groups as follows: I: control group; II: MTX group; III: CLG+MTX group. In the MTX group; malondialdehyde (MDA) content was found to be increased, whereas superoxide dismutase (SOD), catalase (CAT) activities, and glutathione (GSH) content were decreased. On the other hand, CLG markedly attenuated the elevated MDA content and prevented the deleterious effects of MTX on oxidative stress markers. MTX caused severe loss of Purkinje cells and apoptotic cell death in the cerebellum. The CLG administration before MTX treatment significantly reduced Purkinje cell damage and the expression of apoptotic cells. In conclusion, our results demonstrate that chlorogenic acid treatment may protect the impairment of oxidative stress and ameliorate MTX-induced cerebellar damage at biochemical and histological levels.
已有多项研究充分证实,氧化应激在甲氨蝶呤(MTX)引起的各种器官损伤发病机制中起作用。许多药物已在实验中进行了测试,以减少或抑制氧化应激。本研究旨在确定绿原酸(CLG)对 MTX 诱导的大鼠小脑损伤的可能保护作用。大鼠被随机分为三组:I:对照组;II:MTX 组;III:CLG+MTX 组。在 MTX 组中,发现丙二醛(MDA)含量增加,而超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性和谷胱甘肽(GSH)含量降低。另一方面,CLG 显著减弱了 MDA 含量的升高,并防止了 MTX 对氧化应激标志物的有害影响。MTX 导致小脑浦肯野细胞严重丢失和细胞凋亡。在 MTX 治疗前给予 CLG 给药可显著减轻浦肯野细胞损伤和凋亡细胞的表达。总之,我们的结果表明,绿原酸处理可能在生化和组织学水平上保护氧化应激损伤并改善 MTX 诱导的小脑损伤。