Pretreatment with Pyridostigmine Bromide Does not Induce Cellular Toxicity

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.