ABSTRACT
OBJECTIVE: To investigate the inflammatory mechanism of chlorpyrifos-induced lung injury in rats. METHODS: Specific pathogen free SD rats were randomly divided into control and low-, medium-and high-dose groups, 8 rats in each group. Rats were exposed to 48% chlorpyrifos by continuous oral administration for 28 consecutive days, once a day, with the doses of 0.0, 4.1, 8.2 and 16.3 mg/kg body mass. After the exposure, the enzyme-linked immunosorbent assay was used to detect the level of tumor necrosis factor-α(TNF-α) and interleukin-1(IL-1) in rat lung tissue. The expression of high mobility group protein-1(HMGB1) and nuclear transcription factor-κB(NF-κB) was detected by immunohistochemistry and Western blotting, respectively. RESULTS: The activity of the rats decreased after exposure in the low-, medium-and high-dose groups compared with the control group. The rats in the medium and high dose groups increased salivation, nasal secretions, and difficulty breathing. The rats in the high dose group also developed diarrhea, muscle tremor, unstable gait, as well as muscarinic and nicotinic symptoms. After the exposure, the lung tissues of rats in the low-, medium-and high-dose groups showed different degrees of inflammation, which increased in a dose-dependent manner; the body mass of rats in the 3 dose groups was lower than that in the control group(all P values were <0.05), and the body mass of rats decreased with the increase of chlorpyrifos dose(all P values were <0.05). The levels of TNF-α, IL-1 and the relative expression of HMGB1, NF-κB were higher in the 3 dose groups than those in the control group(all P values were <0.05), and the levels of TNF-α, IL-1 and the relative expression of HMGB1 increased with the increasing exposure dose(all P values were <0.05). CONCLUSION: Chlorpyrifos can activate the NF-κB signaling pathway and eventually induce the macrophages to secrete large amount of TNF-α and IL-1, resulting in lung inflammation and injury in rats. The effect of chlorpyrifos has a dose-effect relationship.