The dysfunction of ATPases due to impaired mitochondrial respiration in phosgene-induced pulmonary edema.
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.
Qin
Xu-Jun
XJ
Department of Toxicology, The Fourth Military Medical University, 17 Changle West Road, Xi'an 710032, China.
Li
Ying-Na
YN
Liang
Xin
X
Wang
Peng
P
Hai
Chun-Xu
CX
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D019069:Cell Respiration / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010705:Phosgene / Q000633:toxicity*; D011654:Pulmonary Edema / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
D000975:Antioxidants; D010705:Phosgene; D000251:Adenosine Triphosphatases