Effects of oral administration of tin and zinc protoporphyrin on neonatal and adult rat tissue heme oxygenase activity.
The purpose of this study was to investigate if oral metalloporphyrin treatment could suppress intestinal heme oxygenase (HO) activity and thus prevent HO-mediated heme degradation in this organ. Six hours after a single 40 mumol/kg oral dose of tin protoporphyrin (TP), zinc protoporphyrin (ZP), or heme to adult rats, no significant difference in the HO activity of the intestine was observed relative to control tissues. Moreover, the activity was not inhibited by in vitro exposure to 40 microM TP or ZP. Liver and spleen HO activity was also not significantly inhibited in vivo after oral administration of metalloporphyrins; however, in vitro exposure to TP or ZP decreased the HO activity of preparations from these organs significantly. Like adults, the intestinal HO activity of neonates was not inhibited effectively by oral administration of either metalloporphyrin. The results of subsequent in vitro exposure of control neonatal tissue preparations to ZP or TP was similar to those using adult tissue preparations. Even at 100 microM, only ZP seemed to have some in vitro inhibitory effect on the intestinal HO of suckling rats. We conclude that intestinal HO is less inhibitable by TP or ZP reaching the intestine via the stomach in concentrations at least 30-fold greater than those achieved after parenteral 40 mumol/kg doses, which cause significant hepatic and splenic HO inhibition. Intestinal absorption and enterohepatic circulation of heme, TP, and ZP do not seem to occur in amounts sufficient to consistently and significantly affect HO activity in liver or spleen.
Vreman
H J
HJ
Department of Pediatrics, Stanford University School of Medicine, California 94305.
Hintz
S R
SR
Kim
C B
CB
Castillo
R O
RO
Stevenson
D K
DK
D000284:Administration, Oral; D000375:Aging / Q000378:metabolism*; D000818:Animals; D005260:Female; D006418:Heme / Q000008:administration & dosage / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008665:Metalloporphyrins; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D011166:Porphyrins / Q000378:metabolism*; D011524:Protoporphyrins / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D008665:Metalloporphyrins; D011166:Porphyrins; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D006418:Heme; C032628:tin protoporphyrin IX; D006899:Mixed Function Oxygenases; D006419:Heme Oxygenase (Decyclizing)