Phosgene is a toxic gas that is widely used in modern industry, and its inhalation can cause severe
pulmonary edema. There is no effective clinical treatment because the mechanism of
phosgene-induced
pulmonary edema still remains unclear. Many studies have demonstrated that the Na(+)/K(+)-
ATPase plays a critical role in clearing
pulmonary edema and the inhibition of Na(+)/K(+)-
ATPase protein expression has been found in many other
pulmonary edema models. In the present study, after the mice were exposed to
phosgene, there was serious
pulmonary edema, indicating the dysfunction of the
ATPases in mice. However, in vitro
enzyme study showed that there were increases in the activities of the Na(+)/K(+)-
ATPase and Ca(2+)-
ATPase. Further investigation showed that the
ATP content and mitochondrial respiratory control ratio (RCR) in the lungs decreased significantly. The oxidative stress product,
malondialdehyde (MDA), increased while the
antioxidants (GSH, SOD, and TAC) decreased significantly. These results indicate that mitochondrial respiration is the target of
phosgene. The dysfunction of
ATPases due to impaired mitochondrial respiration may be a new mechanism of
phosgene-induced
pulmonary edema.