Signaling of apoptotic lung injury by lipid hydroperoxides.
BACKGROUND
Acute lung injury is common after shock and sepsis, but the pathophysiology is unclear. Lipid hydroperoxide products including 4-hydroxynonenal (HNE) increase significantly during these insults and may induce apoptosis. This study investigates the role of pathophysiologic concentrations of HNE on isolated lung biophysical function and apoptosis.


METHODS
Male Sprague-Dawley rat lungs were isolated and perfused with Krebs-Henseleit buffered solution for 120 minutes. Hydroxynonenal (50 micromol/L) or vehicle was added to the perfusate at 60 minutes. Lung elastance and perfusion pressure were determined. Perfusate glutathione and lactate dehydrogenase were determined at 30-minute intervals. Genomic DNA was extracted for electrophoretic determination of apoptotic laddering.


RESULTS
There were no differences in any parameter measured before HNE infusion. Lung edema increased significantly with HNE infusion; a trend increase in lung elastance and perfusion pressure was noted. DNA laddering characteristic of apoptosis was noted in HNE-treated lungs that was absent in control animals.


CONCLUSIONS
Lipid hydroperoxide products formed during shock or sepsis may be causally related to lung injury. Low concentrations of a candidate metabolite, HNE, appear to induce significant lung injury and apoptosis, which may partially mediate lung injury during shock and sepsis.
Compton
C N
CN
Department of Surgery, Wayne State University School of Medicine, Detroit, Michigan, USA.
Franko
A P
AP
Murray
M T
MT
Diebel
L N
LN
Dulchavsky
S A
SA
D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D008168:Lung / Q000166:cytology / Q000473:pathology; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology
D000447:Aldehydes; D015853:Cysteine Proteinase Inhibitors; C027576:4-hydroxy-2-nonenal