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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Effect of carbon monoxide on the cytochrome P-450-mediated activation of 4-ipomeanol by the isolated perfused rabbit lung.

4-Ipomeanol is a naturally occurring toxin that induces lesions in the lung following its activation to an alkylating metabolite by the pulmonary cytochrome P-450 system. The aim of this study was to determine if an environmentally relevant concentration of carbon monoxide could inhibit the activation of 4-ipomeanol and prevent the associated toxic sequelae in the isolated perfused rabbit lung. The lungs of male New Zealand rabbits were removed and perfused with [14C]-4-ipomeanol for 2 h starting with an initial concentration of 0.1 mM. Lungs were ventilated with either air (control) or 7.5% CO/20% O2. 4-Ipomeanol-derived covalent binding was identical in the control and carbon monoxide treatment groups. Lungs perfused with 4-ipomeanol and ventilated with air or 7.5% CO/20% O2 both displayed alveolar type II cell hyperplasia and alveolar macrophage infiltration. Surprisingly, there was no histological evidence of Clara cell damage in any of the 4-ipomeanol-perfused lungs. These results suggest that the isozymes of pulmonary cytochrome P-450 that act in concert to metabolize 4-ipomeanol are relatively insensitive to inhibition by carbon monoxide.[1]

References

  1. Effect of carbon monoxide on the cytochrome P-450-mediated activation of 4-ipomeanol by the isolated perfused rabbit lung. Trela, B.A., Carlson, G.P., Turek, J., Rebar, A., Mathews, J.M. Journal of toxicology and environmental health. (1989) [Pubmed]
 
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