Joshi Apurva Kumar R, Rajini P S
Food Protectants and Infestation Control Department, Central Food Technological Research Institute (CSIR Laboratory), Mysore 570020, India.
Exp Toxicol Pathol. 2012 Jan;64(1-2):115-20. doi: 10.1016/j.etp.2010.07.003. Epub 2010 Jul 31.
The purpose of this study was to investigate the involvement of acetylcholinesterase (AChE) inhibition in hyperglycemic and stressogenic effects of monocrotophos in rats. Oral administration of monocrotophos (1.8 mg/kg b.w., 1/10 LD(50)) caused reversible hyperglycemia in rats with peak increase occurring at 2 h following administration. The hyperglycemic outcome at 2 h was accompanied by significant inhibition of acetylcholinesterase (AChE) activity in brain (84%), adrenal (68%) and liver (53%) and stressogenic effects as revealed by marked increase in plasma corticosterone (102%) and liver tyrosine aminotransferase (TAT) (104%) activity. At 4 h following administration, there was normalization of hyperglycemia and hypercorticosteronemia, marginal attenuation of liver TAT activity and marked increase in liver glycogen content, without spontaneous reactivation of AChE activity in the organs studied. Interestingly, pre-treatment of rats with acetylcholine (ACh) receptor antagonists-atropine sulfate and methyl atropine nitrate offered significant protection against hyperglycemia, hypercorticosteronemia and increased liver TAT activity induced by monocrotophos. Our results clearly demonstrate the involvement of AChE inhibition in hyperglycemia and stressogenic effects of monocrotophos in rats following acute exposure. Protection offered by both, general and peripheral ACh antagonists provide further evidence for the involvement of peripheral AChE inhibition in the monocrotophos-induced effects.
本研究的目的是调查乙酰胆碱酯酶（AChE）抑制在久效磷对大鼠的高血糖和应激效应中的作用。口服久效磷（1.8毫克/千克体重，1/10 LD(50)）可导致大鼠出现可逆性高血糖，给药后2小时血糖升高达到峰值。给药后2小时的高血糖结果伴随着脑（84%）、肾上腺（68%）和肝脏（53%）中乙酰胆碱酯酶（AChE）活性的显著抑制以及应激效应，表现为血浆皮质酮（102%）和肝脏酪氨酸转氨酶（TAT）（104%）活性显著增加。给药后4小时，高血糖和高皮质酮血症恢复正常，肝脏TAT活性略有减弱，肝脏糖原含量显著增加，而在所研究的器官中AChE活性未自发恢复。有趣的是，用乙酰胆碱（ACh）受体拮抗剂硫酸阿托品和硝酸甲基阿托品对大鼠进行预处理，可显著保护其免受久效磷诱导的高血糖、高皮质酮血症和肝脏TAT活性增加的影响。我们的结果清楚地证明了AChE抑制在久效磷急性暴露后对大鼠的高血糖和应激效应中的作用。全身性和外周性ACh拮抗剂提供的保护进一步证明了外周AChE抑制参与了久效磷诱导的效应。
