Effect of N-acetylcysteine on time- dependent biochemical and oxidative changes after acute diisopropyl phosphorofluoridate poisoning in mice

Jebin Jacob John, N. L. Gujar, R. Bhattacharya, G. Prasad
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Abstract

Objective: The aim of the study was to investigate the effect of an antioxidant, viz., N -acetylcysteine (NAC) against various biochemical and oxidative changes caused by acute diisopropyl phosphorofluoridate (DFP) poisoning in mice. Materials and Methods: Effect of NAC (150 mg/kg) alone or in conjunction with atropine (10 mg/kg; 0 min), and/or 2-PAM (30 mg/kg; 0 min) on (i) LD 50 of DFP, (ii) time for onset of signs and symptoms, and death after lethal doses of DFP, and (iii) time- dependent biochemical and oxidative damage after 0.50 LD 50 DFP was investigated in Swiss albino mice. Results: NAC (-60 min) did not confer any additional protection against DFP when measured by protection index (ratio of LD 50 of DFP in protected and unprotected animals). However, NAC (-60 min, 0 min or +5 min) with atropine/ and or 2-PAM significantly delayed the onset of signs and symptoms, and time of death after 2.0 LD 50 DFP. Further, NAC (-60 min) augmented the efficacy of atropine and 2-PAM in normalizing the butyrylcholinesterase and reduced glutathione levels in plasma, and acetylcholinesterase, malondialdehyde, glutathione peroxidase, catalase, and superoxide dismutase levels in brain. Conclusion: The study indicates beneficial role of NAC in mitigating the toxicity of OP.
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n -乙酰半胱氨酸对小鼠急性氟化磷二异丙酯中毒后时间依赖性生化和氧化变化的影响
目的:研究抗氧化剂N -乙酰半胱氨酸(NAC)对小鼠急性氟化磷二异丙酯(DFP)中毒引起的各种生化和氧化变化的影响。材料与方法:NAC (150mg /kg)单用或与阿托品(10mg /kg;0分钟),和/或2-PAM (30mg /kg;(i) DFP的ld50, (ii) DFP致死剂量后出现症状和体征的时间,以及死亡的时间,以及(iii)在瑞士白化小鼠中研究0.50 ld50 DFP后的时间依赖性生化和氧化损伤。结果:NAC (-60 min)对DFP的保护指数(保护动物和未保护动物DFP的ld50比)没有任何额外的保护作用。然而,NAC(-60分钟,0分钟或+5分钟)与阿托品/和/或2-PAM显著延迟症状和体征的出现,以及2.0 LD 50 DFP后的死亡时间。此外,NAC(-60分钟)增强了阿托品和2-PAM在恢复血浆中丁基胆碱酯酶和降低血浆中谷胱甘肽水平以及乙酰胆碱酯酶、丙二醛、谷胱甘肽过氧化物酶、过氧化氢酶和超氧化物歧化酶水平方面的功效。结论:NAC对OP的毒性有一定的缓解作用。
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