Neurochemistry Laboratory, Department of Neurological Sciences, Christian Medical College, Vellore, India.
Neurotoxicology. 2012 Mar;33(2):156-61. doi: 10.1016/j.neuro.2012.01.008. Epub 2012 Jan 23.
Neurotoxicity of organophosphate pesticide poisoning, a lead cause of death in South Asia, has not been clearly elucidated. Organophosphates inhibit acetylcholinesterase and neurotoxicity is primarily a result of acetylcholine induced hyperactivation in different regions of the brain. Neurotoxicity also results from oxidative stress induced by acetylcholinesterase inhibition in the brain. Determining the severity of acetylcholinesterase inhibition that induces oxidative damage may help in developing strategies that protect the brain from organophosphate induced toxicity.
To determine the level of acetylcholinesterase inhibition that induces oxidative stress in the brain following organophosphate pesticide poisoning.
Brains of rats subject to acute monocrotophos poisoning (0.8 LD(50) by gavage) were assessed for acetylcholinesterase activity, antioxidant response and oxidative damage 2.5 and 8h after poisoning and on recovery from poisoning 24h later after poisoning. Assessments were made in the cortex, striatum and hippocampus, cholinergic rich regions and cerebellum, targets of organophosphate pesticide poisoning. Analysis was in comparison to non poisoned controls.
High acetylcholinesterase activities were noted in striatum followed by hippocampus, cerebellum and cortex. Acute severe monocrotophos poisoning inhibited acetylcholinesterase 87% in striatum, 67% in hippocampus, 58% in cerebellum, 53% in cortex and increased glutathione levels significantly in all brain regions 2.5h after poisoning. Significant lipid peroxidation and antioxidant enzymes were induced 8h after poisoning, directly correlated to high acetylcholinesterase inhibition (>67%). Recovery from monocrotophos poisoning was associated with absence of lipid peroxidation in the brain although acetylcholinesterase inhibition persisted.
Neurotoxicity of monocrotophos poisoning is characterized by oxidative damage in regions of the brain that exhibit high acetylcholinesterase activity and severe acetylcholinesterase inhibition. Recovery from poisoning is associated with prolonged induction of antioxidants that protect against oxidative damage.
有机磷农药中毒是南亚地区主要的致死原因之一，其神经毒性尚未得到明确阐明。有机磷会抑制乙酰胆碱酯酶，而神经毒性主要是由于不同脑区的乙酰胆碱诱导过度激活所致。此外，由于脑内乙酰胆碱酯酶抑制导致的氧化应激也会引起神经毒性。确定导致氧化损伤的乙酰胆碱酯酶抑制的严重程度，可能有助于制定保护大脑免受有机磷诱导毒性的策略。
确定有机磷农药中毒后大脑中引起氧化应激的乙酰胆碱酯酶抑制水平。
对经灌胃摄入 0.8 LD 50 （半数致死剂量）单虫脒的大鼠的大脑进行评估，在中毒后 2.5 小时和 8 小时以及中毒后 24 小时恢复后，评估大脑中的乙酰胆碱酯酶活性、抗氧化反应和氧化损伤。评估区域包括富含胆碱能的皮质、纹状体和海马等区域以及小脑等有机磷农药中毒的靶器官。分析结果与未中毒的对照组进行比较。
纹状体中的乙酰胆碱酯酶活性最高，其次是海马、小脑和皮质。急性重度单虫脒中毒使纹状体中的乙酰胆碱酯酶抑制了 87%，海马中的乙酰胆碱酯酶抑制了 67%，小脑中的乙酰胆碱酯酶抑制了 58%，皮质中的乙酰胆碱酯酶抑制了 53%，且所有脑区的谷胱甘肽水平在中毒后 2.5 小时显著升高。8 小时后，出现了明显的脂质过氧化和抗氧化酶，这与高乙酰胆碱酯酶抑制（>67%）直接相关。从单虫脒中毒中恢复与大脑中脂质过氧化的消失有关，尽管乙酰胆碱酯酶抑制仍然存在。
单虫脒中毒的神经毒性特征是大脑中乙酰胆碱酯酶活性高和乙酰胆碱酯酶抑制严重的区域发生氧化损伤。从中毒中恢复与抗氧化剂的长期诱导有关，这些抗氧化剂可防止氧化损伤。
