Pre-treatment with the methanol extract of Withania somnifera prevents Diazinon-induced cardiotoxic effects of organophosphate poisoning

Abstract Organophosphate poisoning represents a major and growing global health problem especially in the developing countries and cardiotoxicity is the major cause of death. Thus, a compelling need to develop novel low cost efficacious agents to manage this condition. Objective To evaluate the methanol extract of Withania somnifera as a pre-treatment agent in the prevention of the cardiotoxic effects of diazinon in Sprague Dawley rats Materials and Methods Twenty one (21) adult rats were randomized to receive 200 mg/kg methanol extract of Withania somnifera (test group), vehicle (negative control) or 200 μg/kg Neostigmine as pre-treatment 30 minutes prior to the oral administration of 200 mg/kg Diazinon. Baseline and post-treatment electrocardiograms (ECGs) were recorded by the Powerlab data acquisition system (ML865 AD instruments, Sydney, Australia). The experimental data were expressed as median ± the inter-quartile range and analysed using the Kruskal – Wallis non-parametric test and followed by Mann–Whitney U post hoc test in cases of significance, which was set at p < 0.05. Statistical Package for Social Sciences (SPSS) version 17 software was used for analysis. Results Pre-treatment with the methanol extract of W. somnifera had significant effect on the following diazinon-induced electrocardiographic changes; RR interval (0.026 (0.007 – 0.065) vs. 0.035 (0.019 – 0.050) vs. 0.090 (0.071 – 0.01), p = 0.031),heart rate (-54.235 (-115.317 – (-19.857)) vs. -−96.136 (-96.472 – (-43.879)) vs. -−174.361 (-189.775 – (-129.469)), p = 0.014), PR interval (0.006 (0.004 – 0.008) vs. 0.003 (0.001 – 0.004) vs. 0.009 (0.006 – 0.015), p = 0.019), QRS interval (0.005 (0.001 – 0.008) vs. -−0.002 (-0.005 – 0.001) vs. 0.007 (0.003 – 0.011), p = 0.023) and ST height (-34.830 (-63.578 – 4.215) vs. -−22.330 (-38.383– (-4.159)) vs. -−73.156 (-214.022– (-52.449)), p = 0.023). It however had no significant effect on the QTc interval changes (-0.005 (-0.011 – 0.003) vs. -−0.005 (-0.015 – 0.065) vs. -−0.021 (-0.060– (-0.006)), p = 0.174). Conclusion The efficacy of pre-treatment with the methanol extract of Withania somnifera was comparable to that of pre-treatment with Neostigmine a commonly used carbamate drug. Thus, it is a potentially viable low cost treatment option for organophosphate poisoning in resource-limited settings.