Overproduction of free radicals and inflammation could lead to maneb (MB)- and paraquat (PQ)-induced toxicity in the polymorphonuclear leukocytes (PMNs). Cyclooxygenase-2 (COX-2), an inducible COX, is imperative in the pesticides-induced pathological alterations. However, its role in MB- and PQ-induced toxicity in the PMNs is not yet clearly deciphered. The current study explored the contribution of COX-2 in MB- and PQ-induced toxicity in the PMNs and the mechanism involved therein. Combined MB and PQ augmented the production of free radicals, lipid peroxides and activity of superoxide dismutase (SOD) in the rat PMNs. While combined MB and PQ elevated the expression of COX-2 protein, activation of nuclear factor-kappa B (NF-κB) and phosphorylation of c-Jun N-terminal kinase (JNK), release of mitochondrial cytochrome c and levels of procaspase-3/9 were attenuated in the PMNs. Celecoxib (CXB), a COX-2 inhibitor, ameliorated the combined MB and PQ-induced modulations in the PMNs. MB and PQ augmented the free radical generation, COX-2 protein expression, NF-κB activation and JNK phosphorylation and reduced the cell viability of cultured rat PMNs and human leukemic HL60. MB and PQ elevated mitochondrial cytochrome c release and poly (ADP-ribose) polymerase cleavage whilst procaspase-3/9 levels were attenuated in the cultured PMNs. MB and PQ also increased the levels of phosphorylated c-jun and caspase-3 activity in the HL60 cells. CXB; SP600125, a JNK-inhibitor and pyrrolidine dithiocarbamate (PDTC), a NF-κB inhibitor, rescued from MB and PQ-induced changes in the PMNs and HL60 cells. However, CXB offered the maximum protection among the three. The results show that COX-2 activates apoptosis in the PMNs following MB and PQ intoxication, which could be linked to NF-κB and JNK signaling.

自由基和炎症的过度产生可能导致多形核白细胞 (PMN) 中的代诺布 (MB) 和百草枯 (PQ) 诱导的毒性。环氧合酶 2 (COX-2) 是一种可诱导的 COX，在农药引起的病理改变中必不可少。然而，它在 PMN 中 MB 和 PQ 诱导的毒性中的作用尚未明确破译。目前的研究探讨了 COX-2 在 MB 和 PQ 诱导的 PMN 毒性中的作用及其所涉及的机制。MB 和 PQ 联合使用可增强大鼠 PMN 中自由基、脂质过氧化物和超氧化物歧化酶 (SOD) 的活性。虽然联合 MB 和 PQ 提高了 COX-2 蛋白的表达、核因子-κ B (NF-κB) 的激活和 c-Jun N-末端激酶 (JNK) 的磷酸化、线粒体细胞色素c的释放PMN 中 procaspase-3/9 的水平减弱。塞来昔布 (CXB) 是一种 COX-2 抑制剂，可改善 PMN 中 MB 和 PQ 诱导的联合调节。MB 和 PQ 增强了自由基生成、COX-2 蛋白表达、NF-κB 活化和 JNK 磷酸化，并降低了培养的大鼠 PMN 和人类白血病 HL60 的细胞活力。MB 和 PQ 升高线粒体细胞色素c释放和聚（ADP-核糖）聚合酶切割，而培养的 PMN 中 procaspase-3/9 水平减弱。MB 和 PQ 还增加了 HL60 细胞中磷酸化 c-jun 和 caspase-3 活性的水平。CXB；SP600125，一种 JNK 抑制剂和吡咯烷二硫代氨基甲酸酯 (PDTC)，一种 NF-κB 抑制剂，从 MB 和 PQ 诱导的 PMN 和 HL60 细胞的变化中解救出来。但是，CXB 提供了三者中最大的保护。结果表明，在 MB 和 PQ 中毒后，COX-2 激活 PMN 中的细胞凋亡，这可能与 NF-κB 和 JNK 信号传导有关。