Tin protoporphyrin inhibits carbon monoxide production in adult mice.
We studied the effect of tin protoporphyrin, a potent inhibitor of heme oxygenase (EC 1.14.99.3), on carbon monoxide (CO) production in mature mice. Measurements of CO production provide a sensitive, noninvasive means of quantitating heme catabolism. CO accumulation in the gas space of closed chambers was decreased by about 25% for mice treated with two 50 nmol/g doses of tin protoporphyrin as compared to saline-treated controls. Calculated rates of CO production were 0.28 +/- 0.07 and 0.40 +/- 0.05 nmol X g-1 X h-1 for mice injected with tin protoporphyrin and saline, respectively (p less than 0.01). When hemin (125 nmol/g) was administered to simulate hemolysis, CO production increased markedly in both saline- and tin protoporphyrin-treated mice. However, the rate of CO production in tin protoporphyrin-treated mice was only 44% that of saline-treated animals (p less than 0.0001). These studies demonstrate that tin protoporphyrin inhibits heme catabolism in both the basal- and heme-loaded states and confirm that this inhibition is at the heme oxygenase step in the heme to bilirubin pathway.
D000818:Animals; D002248:Carbon Monoxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D008665:Metalloporphyrins; D051379:Mice; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D011166:Porphyrins / Q000494:pharmacology*; D011524:Protoporphyrins / Q000494:pharmacology*
D008665:Metalloporphyrins; D011166:Porphyrins; D011524:Protoporphyrins; D006418:Heme; D002248:Carbon Monoxide; C032628:tin protoporphyrin IX; D006899:Mixed Function Oxygenases; D006419:Heme Oxygenase (Decyclizing)