Dept. of Clinical Lab Science, Dongseo University, Jurea 2-dong, Sasang-gu, Busan 617-716, Korea.
Toxicol Res. 2010 Sep;26(3):163-70. doi: 10.5487/TR.2010.26.3.163.
Cyclosporine A (CsA) is a potent immunosuppressor that is widely used in transplant surgery and the treatment of several autoimmune diseases. However, major side effects of CsA such as nephrotoxicity, hepatotoxicity, neurotoxicity and cardiovascular diseases have substantially limited its usage. Although molecular mechanisms underlying these adverse effects are not clearly understood, there is some evidence that suggests involvement of reactive oxygen species (ROS) . In parallel, protective effects of various antioxidants have been demonstrated by many research groups. Extensive studies of CsA-induced nephrotoxcity have confirmed that the antioxidants can restore the damaged function and structure of kidney. Subsequently, there have appeared numerous reports to demonstrate the positive antioxidant effects on liver and other organ damages by CsA. It may be timely to review the ideas to envisage the relationship between ROS and the CsA-induced toxicity. This review is comprised of a brief description of the immunosuppressive action and the secondary effects of CsA, and a synopsis of reports regarding the antioxidant treatments against the ROS-linked CsA toxicity. A plethora of recent reports suggest that antioxidants can help reduce many CsA's adverse effects and therefore might help develop more effective CsA treatment regimens.
环孢素 A(CsA)是一种强效的免疫抑制剂,广泛用于移植手术和几种自身免疫性疾病的治疗。然而,CsA 的主要副作用,如肾毒性、肝毒性、神经毒性和心血管疾病,大大限制了其应用。尽管这些不良反应的分子机制尚不清楚,但有一些证据表明活性氧(ROS)的参与。同时,许多研究小组已经证明了各种抗氧化剂的保护作用。对 CsA 诱导的肾毒性的广泛研究证实,抗氧化剂可以恢复肾脏受损的功能和结构。随后,出现了大量的报告表明 CsA 对肝和其他器官损伤的抗氧化作用是积极的。现在是时候回顾一下 ROS 与 CsA 诱导的毒性之间的关系的观点了。这篇综述简要描述了 CsA 的免疫抑制作用和次要作用,以及关于抗氧化剂治疗与 ROS 相关的 CsA 毒性的报告摘要。最近的大量报告表明,抗氧化剂可以帮助减少 CsA 的许多不良反应,因此可能有助于开发更有效的 CsA 治疗方案。