Effect of chronic chlorpyrifos exposure on diaphragmatic muscle contractility and MHC isoforms in adult rats

Object Chlorpyrifos (CPF) is an organophosphate insecticide widely used in crop applications. It exerts its toxicity by inhibiting acetylcholinesterase (AChE) at cholinergic synapses. This study aims to investigate the impact of repeated dietary exposure to CPF during adulthood on the contractile performance of the diaphragm and hormonal regulation in male rats. Methods Three groups of 10 Sprague-Dawley rats were exposed daily to a diet mixed either with a vehicle (control group), a low dose of CPF (1 mg/kg/day; CPF1 group), or a higher dose of CPF (5 mg/kg/day, CPF5 group), for 6 consecutive weeks. Results CPF exposure at both doses increased the twitch tension, time to peak tension, half-relaxation time, and fatigability index of the diaphragm. The myofibrillar protein content was not affected in CPF1 group but increased in CPF5 group compared to controls. Alterations in the myosin heavy chain (MHC) isoforms expression were observed in CPF1 group with increased expression of fast-twitch MHC IIa isoform without any significant modifications in the expression of the different MHC isoforms in CPF5 group. Independent of the used doses, CPF exposure induced a decrease in the testosterone level and an increase in the serum corticosterone and growth hormone levels. Conclusion Chronic exposure of adult male rats to CPF is associated with increased diaphragm contractile performance and fatigability which could be related to perturbations in anabolic and catabolic hormonal balance, and/or possible modification in the excitation-contraction coupling mechanism. This finding provides a deeper insight into the respiratory diaphragm muscle dysfunction associated with long-term dietary CPF exposure.