Lung injury in Fischer but not Sprague-Dawley rats after short-term hyperoxia.
The Fischer rat is known for its susceptibility to develop liver necrosis when challenged with paraquat (Smith et al., J. Pharmacol. Exp. Ther. 235: 172-177, 1985). We postulated that other organs, specifically the lung, may also be more susceptible to injury and examined whether lungs from Fischer (F) rats were injured more easily when challenged with active oxygen species than Sprague-Dawley (SD) rat lungs. We aimed to investigate whether increased susceptibility to oxidant injury was related to differences in lung antioxidant defenses. Perfused lungs from both rat strains were challenged by addition of H2O2 to the perfusate or by short-term hyperoxic ventilation. To assess nonoxidant modes of lung injury, we examined lung responses after exposure to protamine sulfate or neutrophil elastase. Intravascular H2O2 or 3 h in vitro hyperoxia caused lung edema in F but not SD rats, and elastase injured F rat lungs more than the lungs from SD rats. Protamine, however, injured the lungs from both strains to a similar degree. Catalase, but not superoxide dismutase or allopurinol, protected F rat lungs against edema, resulting from 3 h in vitro hyperoxia. The lung homogenate levels for reduced glutathione or conjugated dienes and the activities of lung tissue catalase, glutathione peroxidase, and cytochrome P-450 were not different between the two strains. Lung tissue ATP levels, however, were lower in F than in SD rats. Although the F rat strain appears to have an altered oxidant-antioxidant defense balance, the exact cause of the greater susceptibility to oxidant stress of the F rat strain remains elusive.
He
L S
LS
Cardiovascular Pulmonary Research Laboratory, University of Colorado Health Sciences Center, Denver 80262.
Chang
S W
SW
Ortiz de Montellano
P
P
Burke
T J
TJ
Voelkel
N F
NF
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002374:Catalase / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D010100:Oxygen / Q000633:toxicity*; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000494:pharmacology
D000493:Allopurinol; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D010100:Oxygen