Ahmed Tanzeel, Tripathi Ashok K, Suke Sanvidhan G, Kumar Vivek, Ahmed Rafat S, Das Shukla, Banerjee Basu Dev
Environmental Biochemistry and Immunology Laboratory, Department of Biochemistry, University College of Medical Sciences and G.T.B. Hospital (University of Delhi), Dilshad Garden, Delhi 110 095, India.
Toxicol In Vitro. 2009 Oct;23(7):1319-25. doi: 10.1016/j.tiv.2009.07.016. Epub 2009 Jul 14.
Malathion exerts cholinergic effects at high doses. However, a consequence of low dose (non-cholinergic) exposure causes immunotoxicity and oxidative stress. Hence, this study was designed to find out (i) the cytotoxic and apoptotic effects of cholinergic and non-cholinergic doses of malathion using cultured peripheral blood mononuclear cells (PBMCs) and (ii) the role of GSH and HSP27 and (iii) protective effects of N-acetylcysteine (GSH inducer) and curcumin (HSP27 inducer). In low doses, malathion caused mild depletion of GSH, threefold increase in HSP27 level and a range bound cytotoxicity and apoptosis of PBMC. In contrast, cholinergic dose exposures caused severe GSH depletion and exhibited dose dependent cytotoxicity and necrosis without any significant effect on HSP27 levels. Curcumin increased the levels of HSP27 in PBMC only in presence of low doses and not at high doses of malathion. Both NAC and curcumin were able to prevent malathion-mediated apoptosis of PBMC effectively at non-cholinergic doses and at this concentration of malathion, HSP27 induction keeps apoptosis and GSH depletion under control. Also NAC and curcumin may act as potential therapeutic agents to prevent malathion-induced immunotoxicity.
高剂量时，马拉硫磷会产生胆碱能效应。然而，低剂量（非胆碱能）接触的一个后果是会导致免疫毒性和氧化应激。因此，本研究旨在查明：（i）使用培养的外周血单个核细胞（PBMCs），研究胆碱能和非胆碱能剂量的马拉硫磷的细胞毒性和凋亡作用；（ii）谷胱甘肽（GSH）和热休克蛋白27（HSP27）的作用；（iii）N-乙酰半胱氨酸（GSH诱导剂）和姜黄素（HSP27诱导剂）的保护作用。低剂量时，马拉硫磷会导致GSH轻度消耗，HSP27水平增加三倍，并导致PBMC出现一定范围的细胞毒性和凋亡。相比之下，胆碱能剂量暴露会导致严重的GSH消耗，并表现出剂量依赖性细胞毒性和坏死，而对HSP27水平没有任何显著影响。仅在低剂量而非高剂量马拉硫磷存在的情况下，姜黄素会增加PBMC中HSP27的水平。在非胆碱能剂量下，NAC和姜黄素均能有效预防马拉硫磷介导的PBMC凋亡，在此马拉硫磷浓度下，HSP27的诱导可控制凋亡和GSH消耗。此外，NAC和姜黄素可能作为潜在的治疗剂来预防马拉硫磷诱导的免疫毒性。
