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Pretreatment with Pyridostigmine Bromide Does not Induce Cellular Toxicity

机译：溴吡啶斯的明的预处理不会引起细胞毒性

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Soldiers are exposed to multiple stress conditions adverse psychological, physico-chemical and environmental conditions during warfare which can result in significant physical and chemical alterations in the biological system. The effects of carbamate (pyridostigmine bromide, PB) pretreatment prior to physiological stress and organophosphorous compound, DFP (diisopropylfluorophosphate) exposure have been investigated on rats. This study attempts to decipher the level of cellular toxicity imparted by PB pretreatment by assessing drug efflux transportation of the PB or DFP and possible genotoxicity with respect to chromosomal aberrations, in addition to total antioxidant status (TAS) of blood under such circumstances. Total antioxidant status was observed to be more than 50% potentiated with sign-free dose of PB. Immunohistochemical studies show that drug efflux transporter P-glycoprotein receptors were not quantitatively upregulated by physical stress or hyperthermia or hypothermia or sign-free dosage (0.075 mg/Kg after intramuscular injection) of the xenobiotic pyridostigmine bromide. Treatment with high doses (8-16mg/ml) of PB on alternate days for a week caused 10 -20% increase in the receptor count, indicating the toxicity level. Further, sign-free dose of pyridostigmine does not induce genotoxicity as far as chromosomal breakage is concerned. In silico docking studies show that the pyridostigmine molecule binds with maximum affinity to asparagine(1235), threonine(1199) and arginine(1229) in the C-terminal half of the P-glycoprotein. So, pretreatment with sign-free dose of pyridostigmine bromide offers sufficient protection from stress against organophosphorous DFP exposure as observed from these molecular studies and does not significantly alterP-glycoprotein receptors quantitatively.
机译：战争期间，士兵面临多种压力条件，不利的心理，物理化学和环境条件，可能导致生物系统发生重大的物理和化学变化。在大鼠身上研究了氨基甲酸酯（溴化吡啶斯的明溴化物，PB）在生理应激和有机磷化合物，DFP（二异丙基氟磷酸盐）暴露之前的预处理效果。这项研究试图通过评估PB或DFP的药物外排转运，以及在这种情况下血液的总抗氧化剂状态（TAS）之外，还通过对染色体畸变的可能的遗传毒性，来解释PB预处理所赋予的细胞毒性水平。使用无痕量的PB可以增强总抗氧化剂状态50％以上。免疫组织化学研究表明，外源性吡啶并斯的明溴化物的物理应激或体温过高或体温过低或无体征剂量（肌肉注射后为0.075 mg / Kg）均未定量上调药物外排转运蛋白P-糖蛋白受体。隔天使用高剂量（8-16mg / ml）PB进行治疗一周，会导致受体数量增加10 -20％，表明毒性水平。此外，就染色体断裂而言，无符号剂量的吡啶斯的明不会引起遗传毒性。在计算机对接研究中显示，吡啶斯的明分子以最大亲和力与P-糖蛋白C端一半的天冬酰胺（1235），苏氨酸（1199）和精氨酸（1229）结合。因此，如从这些分子研究中所观察到的那样，用无符号剂量的溴化斯的明胺溴化物进行的预处理可提供足够的保护，使其免受有机磷DFP暴露的压力，并且不会显着改变P-糖蛋白受体的数量。

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