Oxidant-induced alterations in pulmonary microsomal mixed-function oxidation: acute effects of paraquat and ozone.
Pulmonary mixed function oxidations are altered by in vivo exposure to paraquat or ozone. The cytochrome P-450-mediated benzphetamine N-demethylase activity was inhibited by low doses of both oxidants (paraquat, 20 mg/kg, ip; ozone, 1 ppm, 24 hrs). The effect of paraquat did not appear until 4 days after treatment and was still apparent after 2 weeks. The inhibition following exposure to ozone appeared immediately (1 day) and had resolved by one week. Cytochrome b5-mediated lipid desaturation was unaffected by the paraquat treatment and was stimulated by ozone. These alterations in pulmonary mixed function oxidase activities could not be explained by microsomal lipid peroxidation. The concentrations of cytochromes P450 and b5 also did not accurately reflect the altered enzymatic activities. The sites of the paraquat- and ozone-mediated alterations are still unknown.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism; D015786:Cytochromes b5; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors; D010126:Ozone / Q000494:pharmacology*; D010269:Paraquat / Q000494:pharmacology*; D051381:Rats; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism
D003580:Cytochromes; D010126:Ozone; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; C019781:benzphetamine N-demethylase; D013230:Stearoyl-CoA Desaturase; D010089:Oxidoreductases, N-Demethylating; D010269:Paraquat