Sn-protoporphyrin blocks the increase in serum bilirubin levels that develops postnatally in homozygous Gunn rats.
Administration of Sn-protoporphyrin to Gunn rats that are characterized by a genetically determined absence of UDP-glucuronyl transferase activity for bilirubin, 24-30 h after birth, prevented the marked increase in serum bilirubin concentration that occurs in these animals in the postnatal period. A second administration of Sn-protoporphyrin at day 6 maintained serum bilirubin levels in the neonates at the initial level for an additional 6 d. In contrast, in untreated Gunn neonates, serum bilirubin levels increased substantially as expected during the immediate 2-wk period after birth. Studies in adult Gunn rats demonstrated that Sn-protoporphyrin administration diminished biliary bilirubin output, decreased tissue heme oxygenase activity, and did not alter hepatic cytochrome P450 levels. These findings raise the possibility that Sn-protoporphyrin may prove clinically useful in maintaining low levels of serum bilirubin in congenitally jaundiced individuals, such as patients with the Crigler-Najjar syndrome.
D000818:Animals; D000831:Animals, Newborn; D001663:Bilirubin / Q000096:biosynthesis / Q000097:blood*; D003414:Crigler-Najjar Syndrome / Q000201:enzymology; D004195:Disease Models, Animal; D014453:Glucuronosyltransferase / Q000172:deficiency; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors; D006801:Humans; D007231:Infant, Newborn; D007567:Jaundice, Neonatal / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D008665:Metalloporphyrins; D011166:Porphyrins / Q000494:pharmacology*; D011524:Protoporphyrins / Q000494:pharmacology*; D051381:Rats; D011911:Rats, Gunn / Q000097:blood* / Q000235:genetics / Q000254:growth & development; D011922:Rats, Mutant Strains / Q000097:blood*
D008665:Metalloporphyrins; D011166:Porphyrins; D011524:Protoporphyrins; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing); D014453:Glucuronosyltransferase; D001663:Bilirubin