Identification of paraquat-induced lung injury and fibrosis in mice using intraperitoneal injection in different dose and exposure time

Abstract

Objective To explore the effect of paraquat (PQ) on lung injury and fibrosis in mice by using intra-peritoneal administration of different doses and different lengths of exposure time, as well as to establish a more appropriate animal model of lung injury and related fibrosis in a simple operation with favorable reproducibility. Methods Male C57BL/6J mice of 8-10 weeks in the model group were intra-peritoneally administered with different paraquat doses for different lengths of exposure time. There were three fashions of giving PQ: single dosing with different doses (40 mg/kg, 50 mg/kg, or 60 mg/kg), successive dosing every day for 5 d with different doses (10 mg/kg, 12.5 mg/kg, or 15 mg/kg) or intermittent dosing every 4 d for 4 occasions with different doses (20 mg/kg, 22.5 mg/kg, or 25 mg/kg), respectively. Control animals (randomly selected) received an equal volume of saline instead at the same time. Mice were sacrificed at 1 week or 2 weeks after the last exposure. The general physical condition of mice including body weight as well as mortality was monitored daily. Lung static compliance measurement, bronchoalveolar lavage (BAL) fluid samples for cytospin analysis, hydroxyproline assay, and whole left lung sections stained for histological analysis were obtained. Results Both single dosing method and intermittent dosing method with different doses of paraquat could induce acute lung injury in some of mice. The inflammation changes became more serious as the dose increased during the early observation. While during the late observation, the pulmonary fibrosis was found in only a few survival mice. The pathological section showed the fibrotic lesions were mainly found in posterior portion, sub-pleural and peripheral portions of lung. However, the mortality was high in these two methods during early lung injury stage, and lower morbidity of pulmonary fibrosis in late stage. The successive dosing strategy didn’t produced significant differences in pathological changes in lung of mice between different intervals of observation. Conclusion Single dosing with high dosage or intermittent dosing with moderate dosage as a systemic administration strategy was necessary for intra-peritoneal PQ to induce mice acute lung injury. However, the model with low morbidity of pulmonary fibrosis and high mortality during acute injury stage was unsatisfactory one. PQ administration with successive lower doses strategy was not sufficient to induce lung injury as well as pulmonary fibrosis in C57BL/6J mice. Key words: Paraquat; Intraperitoneal injection; Lung injury; Pulmonary fibrosis; Animal model