Abstract

Dichlorophene (DCP) is a halogenated phenolic compound, widely used as fungicide, bactericide and antiprotozoan and also exhibit therapeutic application in several pathological conditions. Taking account of broad use of DCP, its possible effect on spleen (an important immune organ) was investigated in this study. Male albino rats were treated with graded doses of DCP (10%, 20% and 30% of LD50) and spleen and blood were obtained at 24, 48 and 72 hours post treatment. Oxidative stress parameters, proinflammatory cytokines and protein expression of aryl hydrocarbon receptor (AhR), indoleamine-2, 3-Dioxygenase 1 (IDO1) and nuclear factor erythroid 2–related factor 2 (Nrf2) were measured along with histopathological evaluation of spleen. In the present study, DCP perturbs redox status of splenocytes of rats as evidenced by excess ROS generation, lipid peroxidation and nitric oxide production simultaneously with reduction of antioxidant level [glutathione (GSH)] and inhibition of antioxidative enzymes [superoxide dismutase (SOD) and catalase (CAT)]. Two important proinflammatory cytokines, IL-6 and TNF-α were found to be elevated upon DCP treatment. Moreover, DCP also caused activation of AhR and IDO1 with simultaneous down regulation of Nrf2. All these effects of DCP were found to be dose and duration dependent. DCP also affects the spleen micro-architecture in the present study and these alterations were more prominent in high dose group at 72 hours post treatment. Taken together, all these results suggested that DCP induces oxidative stress and also increases proinflammatory cytokine levels to mount its toxic effect on spleen.

 抽象的

二氯酚 (DCP) 是一种卤代酚类化合物，广泛用作杀真菌剂、杀菌剂和抗原虫剂，并且在多种病理状况下也具有治疗应用。考虑到 DCP 的广泛使用，本研究调查了其对脾脏（重要的免疫器官）可能的影响。雄性白化大鼠接受分级剂量的DCP（LD50的10%、20%和30%）治疗，并在治疗后24、48和72小时获取脾脏和血液。测量氧化应激参数、促炎细胞因子和芳烃受体 (AhR)、吲哚胺-2, 3-双加氧酶 1 (IDO1) 和核因子红细胞 2 相关因子 2 (Nrf2) 的蛋白表达，并对脾脏进行组织病理学评估。在本研究中，DCP 扰乱大鼠脾细胞的氧化还原状态，表现为过量的 ROS 生成、脂质过氧化和一氧化氮生成，同时降低抗氧化剂水平 [谷胱甘肽 (GSH)] 和抑制抗氧化酶 [超氧化物歧化酶 (SOD) 和过氧化氢酶（CAT）]。两种重要的促炎细胞因子 IL-6 和 TNF-α 在 DCP 治疗后被发现升高。此外，DCP 还引起 AhR 和 IDO1 的激活，同时下调 Nrf2。研究发现 DCP 的所有这些作用均依赖于剂量和持续时间。在本研究中，DCP 还会影响脾脏微结构，这些改变在治疗后 72 小时的高剂量组中更为突出。总而言之，所有这些结果表明 DCP 会诱导氧化应激，并增加促炎细胞因子水平，从而增加其对脾脏的毒性作用。