Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India.
Toxicology. 2010 Nov 9;277(1-3):6-10. doi: 10.1016/j.tox.2010.08.009. Epub 2010 Aug 20.
Acute organophosphate pesticide poisoning is a common medical emergency with high fatality in agricultural communities of Asia. Organophosphate compounds inhibit acetylcholinesterase and prolonged neuromuscular weakness is a major cause of morbidity and mortality of poisoning. Organophosphate pesticide induced muscle weakness may not only arise from inhibition of acetylcholinesterase but also from non-cholinergic pathomechanisms, particularly mitochondrial dysfunction, affecting the production of sufficient ATP for muscle function. This study examined whether muscle weakness in rats subject to monocrotophos toxicity (0.8LD₅₀) was caused by inhibition of ATP synthesis, by oxidative phosphorylation and glycolysis, in addition to inhibition of muscle acetylcholinesterase. Severe muscle weakness in rats following monocrotophos administration was associated with inhibition of muscle acetylcholinesterase (30-60%) but not with reduced ATP production. The rats rapidly recovered muscle strength with no treatment. The ability of rats to spontaneously reactivate dimethoxy phosphorylated acetylcholinesterase and efficiently detoxify organophosphates may prevent severe inhibition of muscle acetylcholinesterase following acute severe monocrotophos poisoning. This may protect rodents against the development of prolonged muscle weakness induced by organophosphates.
急性有机磷农药中毒是亚洲农业社区常见的医疗急症，死亡率很高。有机磷化合物抑制乙酰胆碱酯酶，肌肉神经持续无力是中毒发病率和死亡率的主要原因。有机磷农药引起的肌肉无力不仅可能是由于乙酰胆碱酯酶的抑制，还可能是由于非胆碱能病理机制，特别是线粒体功能障碍，影响肌肉功能所需的足够 ATP 的产生。本研究检查了在受到久效磷毒性（0.8LD₅₀）的大鼠中，肌肉无力是否是由于抑制了 ATP 合成、氧化磷酸化和糖酵解，除了抑制肌肉乙酰胆碱酯酶之外。大鼠在给予久效磷后出现严重的肌肉无力与肌肉乙酰胆碱酯酶抑制（30-60%）有关，但与 ATP 产生减少无关。大鼠在没有治疗的情况下迅速恢复肌肉力量。大鼠自发重新激活二甲氧基磷酸化乙酰胆碱酯酶和有效解毒有机磷的能力可能防止急性严重久效磷中毒后肌肉乙酰胆碱酯酶的严重抑制。这可能保护啮齿动物免受有机磷引起的持续肌肉无力的发展。
