Reduction of chlorpyrifos-induced toxicity in human lymphocytes by selected phosphodiesterase inhibitors

Abstract

One of the most famous and commonly used compounds from organophosphate (OP) family is chlorpyrifos (CP) which is widespreadly used as a powerful insecticide. Previous studies have shown that OPs induce oxidative stress, inflammation and apoptosis by generating the free radicals. The protective effects of three members of phosphodiesterase inhibitor (PDEI) family, including rolipram (RLP), milrinon (MLR) and pentoxifylline (PTX) were evaluated in the human lymphocytes against CP's toxicity. In this case, the level of oxidative stress biomarkers, the viability of the cells and the rate of apoptosis by flow cytometry were investigated. The results of this study revealed that CP makes a significant increase in the level of inflammatory and oxidative stress markers such as meyloperoxidase (MPO), lipid peroxidation (LPO), total thiol molecules (TTM) and total antioxidant potential (TAP), and also makes an enhancement in the rate of apoptosis process. On the other hand, PDEIs and specifically the combination of them restored the negative effects of CP and significantly prevented the apoptosis and oxidative stress imbalance. It is concluded that these PDEIs have positive effects in attenuation, recovery, and protection of CP-induced toxicity in the human lymphocytes.

Keywords: Apoptosis; Chlorpyrifos; Human lymphocytes; Oxidative stress; Phosphodiesterase inhibitors.