The effect of tin (IV)-protoporphyrin-IX on Bilirubin production and excretion in the rat

Tin (IV)-protoporphyrin-IXa (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 umol/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 <0.001). Cumulative excretion over 19 h was reduced 30.8% (p <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 ng/ 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 jig/100 g/min); by 15 h, it fell to 0.024 ± 0.011 ng/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.