Sn-mesoporphyrin suppression of hyperbilirubinemia in EHBR/Eis rats, an animal model of Dubin-Johnson syndrome.
Sn-mesoporphyrin (SnMP), a potent inhibitor of heme oxygenase (HO), controlled hyperbilirubinemia in rats of the mutant strain EHBR/Eis. This mutant strain displays pronounced conjugated hyperbilirubinuria and dark pigmentation of hepatocytes, characteristics of the Dubin-Johnson syndrome. SnMP administered at a dose of 10 mumol/kg body weight produced an immediate decrease in plasma bilirubin concentrations which could be maintained by weekly injections of this synthetic heme analogue. Marked inhibition of HO activity was demonstrated in liver, kidney and spleen but not in brain. These results demonstrate that SnMP can lower plasma bilirubin concentrations for extended periods in a new mutant rat model of Dubin-Johnson syndrome.
Drummond
G S
GS
Rockefeller University Hospital, New York, N.Y. 10021, USA.
Kappas
A
A
D000818:Animals; D001663:Bilirubin / Q000097:blood; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D006932:Hyperbilirubinemia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D007566:Jaundice, Chronic Idiopathic / Q000097:blood / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008665:Metalloporphyrins / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000187:drug effects / Q000201:enzymology
D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; C055421:tin mesoporphyrin; D006419:Heme Oxygenase (Decyclizing); D001663:Bilirubin