Concomitant Effect of Chlorpyrifos and Intranasal Endotoxin Administration on Apoptosis Related Protein Expression in Lung of Mice

Abstract

Pesticides and bacterial endotoxin have been implicated in variety of respiratory dysfunctions. In present study, mice were administered chlorpyrifos at 3 mg/Kg BW/day for 30 days (by oral gavage) and/or challenged with bacterial endotoxin at 80 µg/mice by intranasal route to investigate expression of apoptosis related proteins such as p53, Bax and caspase-3 in lung. The results of immunohistochemistry of lung showed significant increase in number of p53 expressing cells in chlorpyrifos treated mice as compared to control while endotoxin and chlorpyrifos+endotoxin treated mice showed increased number of p53 expressing cells as compared to control and chlorpyrifos treated mice. Chlorpyrifos or endotoxin administration resulted in increased expression of Bax and Caspase-3 while chlorpyrifos treated and endotoxin challenged mice showed synergistic effect on expression of these proteins. From these results, it is concluded that chlorpyrifos and/or endotoxin increased critical apoptosis related proteins such as p53, Bax and Caspase-3 in lung of mice, which may play pivotal role in pathophysiology of pulmonary dysfunctions resulting from exposure to pesticides and endotoxin.

Study of ethion and lipopolysaccharide interaction on lung in a mouse model

“…Pretreatment with ethion also significantly enhanced the LPS induced TLR4 pulmonary expression suggesting synergistic effect of ethion and LPS to activate TLR4. The synergistic interaction of LPS and pesticide affects the cytokine expression [13], apoptosis [14] and lung immunity [15]. The data shows that stress on lung is worsened when ethion is combined with LPS.…”

“…Lipopolysaccharide (LPS), an endotoxin, is an important constituent of cell wall component in Gram negative bacteria that ligates TLR4 to initiate lung inflammation [9]. The studies regarding interaction of LPS and pesticide on cytokine expression [13]; apoptosis [14] and lung immunity [15] suggested synergistic effect of the combination of LPS with pesticide compared to pesticide alone. We have reported that LPS interacts with various classes of pesticides to alter the magnitude of pulmonary damage [2,[16][17][18][19][20][21] as well as genotoxicity [7,22].…”