The effect of intratracheal administration of a surfactant on mortality in a model of murine paraquat poisoning *
"Paraquat lung" which is complicated with paraquat poisoning has been a lethal pulmonary pathology presenting intra-alveolar fibrosis, but an effective therapy has not been developed so far. We hypothesized that the type Ⅱ alveolar cells producing surfactant were damaged by paraquat which was actively accumulated through out the blood by alveolar epithelial cells. To prove this hypothesis, we examined the effect of an intratracheal administration of an artificial lung surfactant (surfactenR, Mitsubishi Tanabe Pharma Corporation, Osaka) on mortality in a model of murine paraquat poisoning. Paraquat was given intramuscularly 3 days after the intratracheal surfactant administration. The mice used were C57BL/6J strain and Balb/C strain. The lethal dose, 50% (LD50), of paraquat was about 28 mg/kg in the C57BL/6J strain and about 9 mg/kg in the Balb/C strain, respectively. Mortalities of paraquat poisoning in both strains of mice improved significantly when the mice were pretreated with the intratracheal surfactant: all of the 36 Balb/C strain mice died less than 7 days after receiving the intramuscular paraquat (20 mg/kg im) , but 18 out of 26 were still healthy after 2 months when the surfactant was given before an administration of paraquat. In the group treated without surfactant, the healthy lungs volume that we calculated from a CT image decreased from day to day in the dying mice. A histopathological examination revealed alveolar hemorrhaging after 7 days. Intraalveolar fibrosis became remarkable after one month, and it was subsequently confirmed in a Masson trichrome stain. Honeycomb lung was also found. In the group treated with surfactant, intraalveolar fibrosis was not found even after two months. Therefore, we conclude that a pretreatment with artificial lung surfactant inhibits paraquat lung, and also improves the survival rate in paraquat poisoning. We should elucidate the mechanism in which paraquat lung is inhibited by artificial lung surfactant, and also examine the clinical application of the surfactant. (Accepted on October 26, 2010)
