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Protection against chemical-induced lung injury by inhibition of pulmonary cytochrome P-450

Journal Article · · Environmental Health Perspectives; (USA)
DOI:https://doi.org/10.2307/3430670· OSTI ID:6034653
;  [1]
  1. Medical Research Council Laboratories, Carshalton Surrey (England)
Protection afforded by trialkyl phosphorothionates against the lung injury caused by trialkyl phosphorothiolates probably results from the inhibition by the P{double bond}S moiety of the thionates, of one or more pulmonary cytochrome P-450 isozymes. The aromatic hydrocarbons p-xylene and pseudocumene also protect against this injury and inhibit some P-450 isozymes, but by a different mechanism. OOS-Trimethylphosphorothionate and p-xylene were compared as protective agents against the effect of OOS-trimethylphosphorothiolate and two other lung toxins ipomeanol and 1-nitronaphthalene that are known to be activated by cytochrome P-450. The effects of these protective compounds, in vivo, on pulmonary cytochrome P-450 activity were also determined. Both compounds inhibited pentoxyresorufin O-deethylase activity, but not ethoxyresorufin O-deethylase. The phosphorothionate was most effective against lung injury caused by the phosphorothiolates and 1-nitronaphthalene, whereas p-xylene was much more effective against ipomeanol. {beta}-Naphthoflavone, which induces pulmonary ethoxyresorufin O-deethylase activity, did not protect against phosphorothiolate or 1-nitronaphthalene injury, and it was only marginally effective in decreasing the toxicity or ipomeanol.
OSTI ID:
6034653
Journal Information:
Environmental Health Perspectives; (USA), Journal Name: Environmental Health Perspectives; (USA) Vol. 85; ISSN 0091-6765; ISSN EVHPA
Country of Publication:
United States
Language:
English