Oral administration of zinc deuteroporphyrin IX 2,4 bis glycol inhibits heme oxygenase in neonatal rats.
Zinc deuteroporphyrin IX 2,4 bis glycol (ZnBG) has been shown to be a potent inhibitor of heme oxygenase (HO) in vitro. Oral administration, which has been minimally effective with other metalloporphyrins, could be clinically advantageous for prevention of neonatal hyperbilirubinemia. Therefore, we examined the effect of oral administration of ZnBG on tissue HO activity and tissue ZnBG concentrations. Suckling rats at 2 weeks of age received ZnBG at 40 mumol/kg BW via gastric gavage. Rats were killed with anesthetic over-dose after 60 min. ZnBG was detected in the portal and systemic circulation (n = 12), and the liver, kidney, spleen, and intestine (n = 8). ZnBG concentrations of 7.9 nmol/g liver and 1.7 nmol/g spleen corresponded to 67 and 72% inhibition of control HO activity (n = 9; p less than 0.0005) respectively.
Vallier
H A
HA
Department of Pediatrics, Stanford University School of Medicine, Calif.
Rodgers
P A
PA
Stevenson
D K
DK
D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D003905:Deuteroporphyrins / Q000008:administration & dosage / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D008099:Liver / Q000201:enzymology; D008665:Metalloporphyrins / Q000494:pharmacology; D051381:Rats; D013154:Spleen / Q000201:enzymology
D003905:Deuteroporphyrins; D008665:Metalloporphyrins; C060750:zinc deuteroporphyrin IX 2,4-bis(glycol); D006419:Heme Oxygenase (Decyclizing)