A germ-free status does not protect from the lethal effects of acute lung damage caused by O,S,S,-trimethyl phosphorodithioate

Abstract

To investigate whether a normal resident microbiological flora of conventional rats influences the lethality of chemical-induced lung damage, the pneumotoxin O,S,S-trimethyl phosphorodithioate (OSSMe, 75 or 100 mg/kg, s.c.) was administered to age-matched conventional and germ-free male F344 rats. Microbiological and serological examinations confirmed the germ-free state of the germ-free rats and showed that no specific lung pathogens were present in the conventional rats. As in conventional rats, clinical symptoms and death of OSSMe-treated germ-free rats resulted from respiratory failure. The germ-free rats were not more resistant, but rather more susceptible to OSSMe than conventional rats. Increases in lung weight and histological examination of lung tissue 3 days after dosing with OSSMe (75 mg/kg, s.c.) showed no differences between germ-free and conventional rats. Despite alterations in their nasopharyngeal flora, death in the conventional rats was probably not caused by bacterial superinfection. The higher susceptibility of germ-free rats to OSSMe can be partly attributed to pharmacokinetic differences, since plasma levels of OSSMe decreased more slowly in germ-free than in conventional rats. It is concluded that germ-free rats are not protected from the lethal consequences of acute chemical-induced lung damage.