Lung-specific induction of heme oxygenase-1 and hyperoxic lung injury.
Heme oxygenase (HO)-1, which catalyzes heme breakdown, is induced by oxidative stress and may protect against oxidative injury. We hypothesized that induction of HO-1 by hemoglobin (Hb) in the lung would protect the rat from pulmonary O2 toxicity. Rats given intratracheal (i.t.) Hb showed lung-specific induction of HO-1 by 8 h by Western analysis. Rats were then pretreated for 8 h before 60 h of exposure to 100% O2 with either IT normal saline, HB, or Hb plus the HO-1 inhibitor tinprotoporphyrin (SnPP). Both the Hb + O2 and Hb + O2 + SnPP animals had less lung injury than normal saline controls as indicated by lower pleural fluid volumes and wet-to-dry weight ratios (P < 0.01). The improvement in injury in the two Hb-treated groups was the same despite a 61% decrease in HO enzyme activity in the Hb + SnPP group after 60 h of O2. In addition, inhibition of HO activity with SnPP alone before O2 exposure did not augment the extent of hyperoxic lung injury. These results demonstrate that IT Hb induces lung HO-1 in the rat and protects against hyperoxia; however, the protection is not mediated by increased HO enzyme activity.
Taylor
J L
JL
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
Carraway
M S
MS
Piantadosi
C A
CA
D000818:Animals; D004790:Enzyme Induction / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005293:Ferritins / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006454:Hemoglobins / Q000008:administration & dosage / Q000494:pharmacology; D018496:Hyperoxia / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D004791:Enzyme Inhibitors; D006454:Hemoglobins; D008665:Metalloporphyrins; D011524:Protoporphyrins; D005293:Ferritins; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase