Pharmacological and biological effects of tin-protoporphyrin on neonatal hyperbilirubinemic Gunn rats.
Our study was undertaken to examine the pharmacological and biological effects of tin-protoporphyrin, a competitive inhibitor of heme oxygenase, on 5- or 6-day-old homozygous (j/j) Gunn rats with hereditary unconjugated hyperbilirubinemia. When j/j neonates were injected subcutaneously with 20 mumol of tin-protoporphyrin/kg of body weight, hepatic heme oxygenase activity decreased to 30% of the initial level 2 h after administration and remained low during the next 46 h. However, the reduction of serum bilirubin was more rapid and transient, reaching the minimum value (40% of the initial level) at 1 h and increasing thereafter at a rate almost comparable to that in nontreated j/j rats. The mortality rate of j/j rats was strikingly reduced by the administration of 1 to 100 mumol of tin-protoporphyrin/kg; the most effective dose was 5 mumol/kg (8% compared with 80% in non-treated j/j rats). However, the protective effect of tin-protoporphyrin on bilirubin cerebellopathy (cerebellar hypoplasia) was less marked than expected. Possible implications of our results are discussed.
Nagae
H
H
Department of Pediatrics, Nagoya University School of Medicine, Japan.
Keino
H
H
Watanabe
K
K
Kashiwamata
S
S
D000818:Animals; D001663:Bilirubin / Q000097:blood; D004195:Disease Models, Animal; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism; D006932:Hyperbilirubinemia / Q000517:prevention & control*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008665:Metalloporphyrins; D008705:Methemalbumin / Q000378:metabolism; D011166:Porphyrins / Q000627:therapeutic use*; D011524:Protoporphyrins / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011911:Rats, Gunn; D011919:Rats, Inbred Strains; D013154:Spleen / Q000201:enzymology
D008665:Metalloporphyrins; D008705:Methemalbumin; D011166:Porphyrins; D011524:Protoporphyrins; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing); D001663:Bilirubin