Abstract
One enzymatic source of free oxygen radical production in lung cells is the cytochromc P450 system. We have reported that a single dose of either endotoxin (E) or cimetidine (C), both inhibitors of hepatic P450 activity, significantly reduces pulmonary oxygen toxicity in lambs. To determine if the in vivo reduction of lung injury could be linked to lung P450 activity, microsomes were isolated from whole blood-free lung, and P450 activity was measured in vitro in 13 oxygen-toxic lambs and in 3 similarly instrumented lambs who breathed air for 3 - 5 days. P450 activity was estimated as the dcmethylation of d-benzphetaminc with subsequent generation of formaldehyde.
The results indicate that in lamb lung 1) hyperoxia increases P450 activity, and 2) both cimetidine and endotoxin block the increase in P450 activity due to oxygen exposure. These studies lend further support to the hypothesis that P450-mediatcd oxygen metabolism may be important in the pathogenesis of pulmonary oxygen toxicity in lambs.
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Liazinski, T., Hicks, P. & France, M. EFFECT OF CIMETIDINE AND ENDOTOXIN ON LUNG MICROSOMAL P450 ACTIVITY IN OXYGEN-TOXIC LAMBS. Pediatr Res 21 (Suppl 4), 215 (1987). https://doi.org/10.1203/00006450-198704010-00291
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DOI: https://doi.org/10.1203/00006450-198704010-00291