The effect of tin (IV)-protoporphyrin-IX on bilirubin production and excretion in the rat.
Tin (IV)-protoporphyrin-IX alpha (tin-heme) may have use in treating neonatal jaundice. To evaluate its effect on bilirubin metabolism, we measured bile-bilirubin excretion in adult, male Sprague-Dawley rats (350-500 g). After a 4-h baseline period, tin-heme (100 mumol/kg) or buffer was injected subcutaneously, and bile was collected for 19 h. Bile flow, bile salt excretion, and bile-bilirubin excretion (averaging 600 +/- 60 ng/100 g/min for all animals) remained stable in the control period. Tin-heme treatment did not alter bile flow or bile salt excretion, but within 2 h bilirubin output was significantly reduced. The nadir of output was 5 h after injection when it was 380 +/- 40 ng/100 g/min (p less than 0.001). Cumulative excretion over 19 h was reduced 30.8% (p less than 0.01). To determine if tin-heme interfered with hepatic uptake or excretion of bilirubin, additional animals were administered intravenous bilirubin at 30 mg/kg/h for 3 h after tin-heme injection. Neither peak bile-bilirubin (37.4 +/- 4.68, control; 38.19 +/- 3.81 micrograms/100 g/min, treated) nor cumulative excretion (87.8 +/- 4.7, control; 88.9 +/- 4.2%, treated) were altered. Biliary excretion of tin-heme was measured under various experimental conditions. When administered alone, maximal excretion was 4 h after injection (4.41 +/- 1.58 micrograms/100 g/min); by 15 h, it fell to 0.024 +/- 0.011 microgram/100 g/min; 20-h cumulative tin-heme excretion in bile was 21.8 +/- 3.1% of the administered dose. Intravenous coadministration of albumin or albumin and bilirubin reduced the peak output but did not alter cumulative excretion of tin-heme. These data indicate that tin-heme reduces endogenous bilirubin formation but does not impair hepatic uptake and excretion. Bile is a major excretory route for tin-heme.
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D001663:Bilirubin / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007567:Jaundice, Neonatal / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008665:Metalloporphyrins; D011166:Porphyrins / Q000494:pharmacology*; D011524:Protoporphyrins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D008665:Metalloporphyrins; D011166:Porphyrins; D011524:Protoporphyrins; C032628:tin protoporphyrin IX; D001663:Bilirubin