Yadav Preeti, Jadhav Sunil E, Kumar Vinesh, Kaul Kirtee K, Pant Satish C, Flora Swaran J S
Division of Pharmacology & Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior, India.
Interdiscip Toxicol. 2012 Mar;5(1):1-8. doi: 10.2478/v10102-012-0001-x.
The effect of 2- pyridine aldoxime methyl chloride (2-PAMCl) and atropine with or without curcumin was investigated in dichlorvos (2,2-dichlorovinyl dimethyl phosphate; DDVP) induced toxicity in rats. Rats were exposed to DDVP (2 mg/kg sub-cutaneously) once daily for the period of 21 days. Post DDVP exposure, rats were further treated with 2-PAMCl (50 mg/kg intramuscular, once daily) + atropine (10 mg/kg, i.m. once daily) with or without curcumin (200 mg/kg; oral; once daily) for further 21 days. We observed a significant increase in lipid peroxidation (LPO), reactive oxygen species (ROS), oxidized glutathione (GSSG), while there was a significant decrease in antioxidant enzymes, brain acetylcholinesterase (AChE) and 5-hydroxy tryptamine (5-HT) activity on DDVP exposure of rats. These alterations were restored significantly by co-administration of 2-PAMCl + atropine in DDVP exposed rats. Curcumin when co-supplemented with 2-PAMCl + atropine also significantly protected serum aspartate aminotransferase (AST) and restored brain AChE activity and 5-HT level in animals sub-chronically exposed to DDVP. Histopathological observations along with biochemical changes in rat blood and tissues revealed significant protection offered by 2-PAMCl + atropine against DDVP. The results indicate that DDVP-induced toxicity can be significantly protected by co-administration of 2-PAMCl + atropine individually, however, curcumin co-supplementation with 2-PAMCl + atropine provides more pronounced protection, concerning particularly neurological disorders.
研究了氯解磷定（2 - 吡啶醛肟甲基氯；2 - PAMCl）和阿托品单独或联合姜黄素对大鼠敌敌畏（2,2 - 二氯乙烯基二甲基磷酸酯；DDVP）诱导毒性的影响。大鼠连续21天每天皮下注射一次敌敌畏（2 mg/kg）。在接触敌敌畏后，大鼠再接受2 - PAMCl（50 mg/kg肌肉注射，每天一次）+阿托品（10 mg/kg，肌肉注射，每天一次），联合或不联合姜黄素（200 mg/kg；口服；每天一次），持续21天。我们观察到，大鼠接触敌敌畏后，脂质过氧化（LPO）、活性氧（ROS）、氧化型谷胱甘肽（GSSG）显著增加，而抗氧化酶、脑乙酰胆碱酯酶（AChE）和5 - 羟色胺（5 - HT）活性显著降低。在接触敌敌畏的大鼠中，联合使用2 - PAMCl +阿托品可显著恢复这些改变。当姜黄素与2 - PAMCl +阿托品联合使用时，也能显著保护亚慢性接触敌敌畏动物的血清天冬氨酸转氨酶（AST），并恢复脑AChE活性和5 - HT水平。大鼠血液和组织的组织病理学观察及生化变化表明，2 - PAMCl +阿托品对敌敌畏具有显著的保护作用。结果表明，单独使用2 - PAMCl +阿托品可显著保护敌敌畏诱导的毒性，然而，姜黄素与2 - PAMCl +阿托品联合使用提供了更显著的保护作用，尤其是在神经紊乱方面。
