The in vitro and in vivo Inhibition of Intestinal Heme Oxygenase by Tin-Protoporphyrin

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Abstract
The effects of tin-protoporphyrin (SnPP) on the activity of heme oxygenase in the epithelium of the proximal region of the small intestine were examined in male Sprague-Dawley rats. A single dose of SnPP (25 µmol/kg body weight) administered either parenterally or by gavage-produced time-dependent decreases in the activity of microsomal heme oxygenase over 24–48 h. Although heme oxygenase activity reverted to normal levels within 24 h after oral dosing, parenteral treatment resulted in substantial (70%) inhibition of the enzyme through at least 48 h after administration of the metalloporphyrin. In vitro, SnPP was shown to be a competitive inhibitor of microsomal heme oxygenase (Ki = 0.017 µM). Tissue tin levels were determined by graphite furnace atomic absorption spectroscopy 48 h after SnPP treatments. Comparable levels of tin were found in the liver and kidney after parenteral treatment (14.34 ± 1.50 and 14.39 ± 0.45 µg/g dry weight, respectively) while only 1.5–3% of these amounts were found in these organs after oral treatment with the metalloporphyrin. These studies establish that the rate-limiting enzyme in the catabolism of heme to bilirubin is inhibited in intestinal epithelium to the same extent as the enzyme is inhibited in other organs.