Ascorbic acid and α-tocopherol as potent modulators of apoptosis on arsenic induced toxicity in rats
Ascorbic acid and α-tocopherol as potent modulators of apoptosis on arsenic induced toxicity in rats
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DOI：
10.1016/j.toxlet.2004.12.003
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发表时间：
2005-04-10
影响因子：
3.5
通讯作者：
Panneerselvam, C
中科院分区：
文献类型：
--
作者：
Ramanathan, K;Anusuyadevi, M;Panneerselvam, C
细胞凋亡或程序性细胞死亡(PCD)是一种受基因调控的细胞、生理和生化自杀机制，在动态平衡的发展和防御中起着至关重要的作用，细胞通过一系列分子相互作用参与自身的死亡。PCD可以受到各种刺激的调节，包括感染性因素或药物。砷是一种可诱导的毒性物质，它通过产生自由基来触发细胞凋亡。由于砷代谢过程中产生的自由基被认为与砷中毒有关，因此了解攻击DNA等重要分子的ROS所造成的有害影响就变得非常重要。本研究旨在探讨维生素C和维生素E对砷中毒大鼠肝细胞凋亡过程的调节作用，以及肿瘤坏死因子-α和半胱氨酸天冬氨酸氨基转移酶-3在其中的作用。选用体重120-150g的Wistar系雄性白化大鼠，随机分为7组。我们观察到，抗坏血酸和α-生育酚通过降低肿瘤坏死因子-α水平和抑制caspase级联反应来选择性地改变DNA损伤的程度，从这些观察中我们强烈相信，目前的维生素补充角度，尽管在动物模型中观察到，将在已经受到影响的人群中具有持续的治疗价值，中和对新出现的砷中毒情景的影响，并可能主动保护那些潜在的易受砷中毒影响的人。(C)2004爱思唯尔爱尔兰有限公司。保留所有权利。
Apoptosis or programmed cell death (PCD) is a genetically regulated cellular, physiological and biochemical Suicidal mechanism that plays a crucial role in the development and defense of homeostasis, in which the cell participates in its own demise via a cascade of molecular interactions. PCD can be modulated by various stimuli including infectious agents or drugs. Arsenic is one among inducible toxic agent that triggers apoptosis via free radical generation. Since the generation of free radicals during the metabolism of arsenic is thought to be involved in arsenic toxicosis, understanding the deleterious effects caused by the ROS that attack the vital molecules like DNA has become important. The present work was conducted to evaluate the regulatory effect exerted by Vitamin C and Vitamin E upon the apoptotic process, which can be assessed by the presence of cells with apoptosis associated DNA breaks and characterize the role of TNF-alpha and caspase-3 in rats intoxicated with arsenic. Male albino rats of wistar strain (120-150 g) were used in this study and are further divided into seven groups. We observed that ascorbate and a-tocopherol selectively altered the extent of DNA damage by reducing TNF-alpha level and inhibiting the activation of caspase cascade, from these observations it is strongly believed that the present vitamins supplementation perspective, though observed in animal model, will have sustainable curative value among the already afflicted populations, neutralizing impact on freshly emerging arsenicosis scenario and possible proactive protection to those potentially susceptible to arsenicals exposure. (c) 2004 Elsevier Ireland Ltd. All rights reserved.