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Effects of inhibition and induction of cytochrome P-450 isozymes on hyperoxic lung injury in rats.

Publication ,  Journal Article
Todd, NW; Hunt, CM; Kennedy, TP; Piantadosi, CA; Whorton, AR
Published in: Am J Respir Cell Mol Biol
August 1992

Pulmonary oxygen toxicity most likely results from excessive production of reactive oxygen species. The role of the cytochromes P-450 in this process is controversial because these enzymes have been reported both to enhance hyperoxic lung injury and to protect from the damaging effects of 100% oxygen. We sought to further determine the role of the cytochromes P-450 in hyperoxic lung injury by inhibiting and inducing pulmonary cytochrome P-450 isozymes in rats. Treatment with the cytochrome P-450 inhibitor cimetidine or 8-methoxypsoralen did not improve survival or reduce lung edema in rats exposed to 100% oxygen. The activity of cytochrome P-450IIB1, the major pulmonary cytochrome P-450 isozyme in rats, was clearly inhibited by 8-methoxypsoralen. beta-Naphthoflavone (beta NF), a selective inducer of cytochrome P-450IA1, was administered in two-dose and five-dose regimens. The two-dose regimen produced significant and sustained induction of cytochrome P-450IA1 activity, but survival in these rats was not improved when exposed to 100% oxygen. In rats treated with five doses of beta NF, a small increase in survival time was found from 71.1 +/- 8.7 to 88.0 +/- 20.2 h; however, there was no difference in the induction of cytochrome P-450IA1 activity between this five-dose regimen and the two-dose regimen. The small improvement in survival after five doses of beta NF is thus unrelated to cytochrome P-450IA1 induction. We conclude that neither inhibition of cytochrome P-450IIB1 activity nor induction of cytochrome P-450IA1 activity protects adult rats against hyperoxic lung injury.

Duke Scholars

Published In

Am J Respir Cell Mol Biol

DOI

ISSN

1044-1549

Publication Date

August 1992

Volume

7

Issue

2

Start / End Page

222 / 229

Location

United States

Related Subject Headings

  • beta-Naphthoflavone
  • Respiratory System
  • Rats, Inbred Strains
  • Rats
  • Oxygen
  • Oxidoreductases
  • Microsomes
  • Methoxsalen
  • Male
  • Lung Diseases
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Todd, N. W., Hunt, C. M., Kennedy, T. P., Piantadosi, C. A., & Whorton, A. R. (1992). Effects of inhibition and induction of cytochrome P-450 isozymes on hyperoxic lung injury in rats. Am J Respir Cell Mol Biol, 7(2), 222–229. https://doi.org/10.1165/ajrcmb/7.2.222
Todd, N. W., C. M. Hunt, T. P. Kennedy, C. A. Piantadosi, and A. R. Whorton. “Effects of inhibition and induction of cytochrome P-450 isozymes on hyperoxic lung injury in rats.Am J Respir Cell Mol Biol 7, no. 2 (August 1992): 222–29. https://doi.org/10.1165/ajrcmb/7.2.222.
Todd NW, Hunt CM, Kennedy TP, Piantadosi CA, Whorton AR. Effects of inhibition and induction of cytochrome P-450 isozymes on hyperoxic lung injury in rats. Am J Respir Cell Mol Biol. 1992 Aug;7(2):222–9.
Todd, N. W., et al. “Effects of inhibition and induction of cytochrome P-450 isozymes on hyperoxic lung injury in rats.Am J Respir Cell Mol Biol, vol. 7, no. 2, Aug. 1992, pp. 222–29. Pubmed, doi:10.1165/ajrcmb/7.2.222.
Todd NW, Hunt CM, Kennedy TP, Piantadosi CA, Whorton AR. Effects of inhibition and induction of cytochrome P-450 isozymes on hyperoxic lung injury in rats. Am J Respir Cell Mol Biol. 1992 Aug;7(2):222–229.

Published In

Am J Respir Cell Mol Biol

DOI

ISSN

1044-1549

Publication Date

August 1992

Volume

7

Issue

2

Start / End Page

222 / 229

Location

United States

Related Subject Headings

  • beta-Naphthoflavone
  • Respiratory System
  • Rats, Inbred Strains
  • Rats
  • Oxygen
  • Oxidoreductases
  • Microsomes
  • Methoxsalen
  • Male
  • Lung Diseases