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在大鼠亚急性敌敌畏中毒期间,毒蕈碱能机制与氧化应激的关系。

The relationship between the cholinergic mechanism of toxicity and oxidative stress in rats during subacute diazinon poisoning.

机构信息

Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Belgrade, Serbia.

School of Medicine, University of Belgrade, Serbia.

出版信息

Toxicol Appl Pharmacol. 2023 Aug 15;473:116598. doi: 10.1016/j.taap.2023.116598. Epub 2023 Jun 16.

DOI:10.1016/j.taap.2023.116598
PMID:37331382
Abstract

Diazinon is an organophosphate pesticide (OP) that has significant potential for accidental and intentional poisoning of wildlife, domestic animals and humans. The aim of the study is to investigate the correlation between cholinesterase activity and oxidative stress parameters in liver and diaphragm by continuous monitoring as a function of time during prolonged use of diazinon. Wistar rats were treated orally with diazinon (55 mg/kg/day): 7, 14, 21 and 28 days. At the end of each period, blood, liver and diaphragm were collected to examine cholinesterase activity and enzymatic/non-enzymatic oxidative stress parameters: superoxide dismutase 1 (SOD1), catalase (CAT), thiobarbituric acid substances (TBARS), protein carbonyl groups. In all four time periods, there was a significant change in acetylcholinesterase (AChE) in erythrocytes and butyrylcholinesterase (BuChE) in blood plasma, CAT in liver and diaphragm and SOD1 in diaphragm. Parameters significantly altered during the cholinergic crisis included: cholinesterases and TBARS in liver and diaphragm and partially SOD1 in liver. Protein carbonyl groups in liver and diaphragm were significantly altered outside the cholinergic crisis. In the liver, there was a very strong negative correlation between BuChE and TBARS in all four time periods and BuChE and CAT on day 7. In the diaphragm, a very strong negative correlation was found between AChE and TBARS at days 7 and 14, and a very strong positive correlation between AChE and SOD1 at days 14, 21 and 28. A better understanding of the relationship between cholinergic overstimulation and oxidative stress may help to better assess health status in prolonged OPs intoxication.

摘要

敌敌畏是一种有机磷农药 (OP),它对野生动物、家畜和人类意外和故意中毒具有很大的潜力。本研究旨在通过连续监测,研究在敌敌畏长期使用过程中,随时间变化胆碱酯酶活性与肝、膈肌氧化应激参数之间的相关性。Wistar 大鼠经口给予敌敌畏(55mg/kg/天):7、14、21 和 28 天。每个时期结束时,采集血液、肝脏和膈肌,以检查胆碱酯酶活性和酶/非酶氧化应激参数:超氧化物歧化酶 1 (SOD1)、过氧化氢酶 (CAT)、硫代巴比妥酸物质 (TBARS)、蛋白羰基。在所有四个时期,红细胞乙酰胆碱酯酶 (AChE) 和血浆丁酰胆碱酯酶 (BuChE)、肝和膈肌 CAT 以及膈肌 SOD1 均发生显著变化。胆碱能危象期间发生显著改变的参数包括:肝和膈肌中的胆碱酯酶和 TBARS,以及部分肝中的 SOD1。肝和膈肌中的蛋白羰基在胆碱能危象之外发生了显著改变。在肝脏中,在所有四个时期中,BuChE 与 TBARS 之间以及第 7 天 BuChE 与 CAT 之间存在很强的负相关。在膈肌中,在第 7 天和第 14 天之间,AChE 与 TBARS 之间存在很强的负相关,在第 14、21 和 28 天之间,AChE 与 SOD1 之间存在很强的正相关。更好地了解胆碱能过度刺激与氧化应激之间的关系可能有助于更好地评估长期有机磷中毒时的健康状况。

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