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

Abstract

Protection afforded by trialkyl phosphorothionates against the lung injury caused by trialkyl phosphorothiolates probably results from the inhibition by the P = 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 of ipomeanol.

• Authors: R D Verschoyle, D Dinsdale
• Journal: Environmental health perspectives (Environ Health Perspect) Vol. 85 Pg. 95-100 (Apr 1990) ISSN: 0091-6765 [Print] United States
• PMID: 2384072 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Carcinogens
• Naphthalenes
• Organothiophosphates
• Organothiophosphorus Compounds
• Terpenes
• Toxins, Biological
• Xylenes
• O,O,S-trimethyl phosphorothioate
• O,S,S-trimethyl phosphorodithioate
• O,O,S-trimethylphosphorodithionate
• 4-xylene
• Cytochrome P-450 Enzyme System
• 1-nitronaphthalene
• Oxidoreductases
• Cytochrome P-450 CYP1A1
• Cytochrome P-450 CYP2B1
• 4-ipomeanol

Topics

• Administration, Oral
• Animals
• Carcinogens (toxicity)
• Cytochrome P-450 CYP1A1
• Cytochrome P-450 CYP2B1
• Cytochrome P-450 Enzyme System (physiology)
• Female
• Lung Diseases (chemically induced, drug therapy, enzymology)
• Naphthalenes (toxicity)
• Organothiophosphates (administration & dosage, pharmacology, therapeutic use, toxicity)
• Organothiophosphorus Compounds (therapeutic use, toxicity)
• Oxidoreductases (physiology)
• Rats
• Terpenes (toxicity)
• Toxins, Biological (toxicity)
• Xylenes (pharmacology, therapeutic use)