Effect of Cold Stress on Pyridostigmine Pretreated Rats Exposed to an Organophosphorous Compound

Context: Pyridostigmine bromide (PB) is a quaternary ammonium compound and has been approved as a pretreatment drug against toxic organophosphorous (OP) compounds. The stressful demands of modern military activity include a broad range of activities at extreme cold temperatures along with various physical activities. Objective: The effect of “sign free” dose of PB (0.075 mg/kg body weight) against a toxic OP compound diisopropyl fluorophosphate (DFP) was reassessed in rats. Electrocardiographic (ECG) studies in hypothermic and pretreatment conditions were undertaken to assess the cardioprotective role of PB. Total Antioxidant Status (TAS) was quantified to assess the degree of oxidative stress imposed under such conditions. Possible protective role of pyridostigmine in rat lymphocytes was also determined.Materials& Methods: TAS was estimated spectrophotometrically and the expression of interferon-γ (IFNγ) was measured by Fluorescence Activated Cell Sorting. ECG was monitored by standard protocol.Results: ECG recording showed that the PR and QT interval progressively increased along with widening of QRS complex. There was a progressive fall in heart rate as the body temperature decreased. TAS significantly decreased (p≤0.001) in hypothermic conditions and when pretreated with sign free dose of PB before cold induction (p≤0.001). Following immunostaining of lymphocytes by FITC conjugated mouse anti-rat IFNγ monoclonal antibody, 9.1% of lipopolysaccharide elicited parent cells showed positive IFNγ expression. Hypothermic stress inhibited IFNγ expression (3.6% of parent cells) which was recovered to 6.8% upon pre-treatment with sign-free dose of pyridostigmine. Conclusion: This study is indicative of a possible protective role of PB against hypothermic stress.