Drug metabolizing enzymes in the rat after inhalation of halothane and enflurane. Different pattern of response in liver, kidney and lung and possible implications for toxicity.
Male Sprague-Dawley rats were exposed in inhalation chambers to halothane and enflurane in concentrations from 50 to 1000 p.p.m. (0.0025 MAC-0.05 MAC) 6 h a day for 3-11 days. No signs of general toxicity were found. There was a normal increase in weight, and normal food consumption, organ to body weight ratios and normal histological findings in liver, kidney and lung. Exposure to 500 p.p.m. (0.05 MAC) of halothane induced the activity of NADPH-cytochrome-c-reductase in the liver, decreased the concentration of cytochrome P-450 in the kidney and decreased all the enzyme concentrations measured in lung microsomes. Exposure to halothane 50 p.p.m. (0.005 MAC) and enflurane produced only minor changes. It is concluded that the inhalation of halothane, in contrast to enflurane, may affect drug metabolism and thereby drug kinetics and toxicity. Halothane may increase its own toxicity by increasing the activity of NADPH-cytochrome-c-reductase in liver. An organ differentiation in enzymatic response was observed.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003573:Cytochrome b Group / Q000378:metabolism; D015786:Cytochromes b5; D004737:Enflurane / Q000494:pharmacology* / Q000633:toxicity; D006221:Halothane / Q000494:pharmacology* / Q000633:toxicity; D007668:Kidney / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D008168:Lung / Q000201:enzymology*; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D009245:NADH Dehydrogenase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D003573:Cytochrome b Group; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D004737:Enflurane; D009245:NADH Dehydrogenase; D006221:Halothane