Intestinal heme oxygenase inhibition and increased biliary iron excretion by metalloporphyrins.
The effects of synthetic metalloporphyrins on heme oxygenase activity in the epithelium of the proximal region of the small intestine were examined both in vitro and in vivo in male Sprague-Dawley rats. Metalloporphyrins, which inhibit hepatic heme oxygenase in vitro, also inhibit intestinal heme oxygenase. Chromium and tin porphyrins are the most potent inhibitors of the intestinal enzyme in vitro. Oral administration of Sn-protoporphyrin (25 mumol/kg body weight) resulted in inhibition of intestinal heme oxygenase; however, no effect was observed on the splenic, hepatic, or renal enzymes. Metal analyses in these tissues showed essentially no intestinal absorption of the metalloporphyrin. Oral administration of Cr-mesoporphyrin (25 mumol/kg body wt) also resulted in inhibition of intestinal heme oxygenase activity. Zinc and manganese mesoporphyrin did not inhibit intestinal heme oxygenase activity when administered orally. Microsomal intestinal heme oxygenase activity was inhibited in a dose-dependent manner by antiserum raised in rabbit against rat hepatic heme oxygenase. The parenteral administration of metalloporphyrin inhibitors of heme oxygenase to bile duct-cannulated rats resulted in a significant increase in iron levels in the bile.
Drummond
G S
GS
Rockefeller University Hospital, New York, New York.
Rosenberg
D W
DW
Kappas
A
A
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D007422:Intestines / Q000187:drug effects / Q000201:enzymology*; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008297:Male; D008652:Mesoporphyrins / Q000494:pharmacology; D008665:Metalloporphyrins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D008652:Mesoporphyrins; D008665:Metalloporphyrins; D006418:Heme; C031468:mesoporphyrin IX; D007501:Iron; D006419:Heme Oxygenase (Decyclizing)