Tin protoporphyrin (SnPP) and analogs are being studied as possible agents for the prevention of neonatal hyperbilirubinemia through inhibition of heme oxygenase. Because SnPP is a photosensitizer, we studied its role in the photogeneration of carbon monoxide (CO) from organic compounds in vitro. Generation of CO occurred in the presence of 5 \iM SnPP and cool white light (19 pW/cnri/nm or 29 W/m2) from SnPP alone, human serum albumin, glucose, histidine, ethanolamine, medium-chain triglycerides, the reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH), and human plasma. More detailed studies with human serum albumin and NADPH established that the photogeneration of CO is nearly linear with time and irradiance. It is curvilinear with respect to the SnPP concentration at the concentrations tested, and it is dependent on the presence of O2 in the reactor headspace. Cool white light generated less CO from human serum albumin and NADPH than equidistantly placed blue and green phototherapy light sources. Comparison of SnPP with other metalloporphyrin heme oxygenase inhibitors indicates that tin mesoporphyrin is most and zinc protoporphyrin least photoreactive.
ABSTRACT. We determined the inhibitory effects of concentrations of tin-and zinc protoporphyrin (1-100 pM) and mesoporphyrin (0.1-10 pM) on the in vitro heme oxygenase (HO) (E.C.1.14.99.3) activity in liver, spleen, and intestine 13, 000 % g tissue supernatants from fasted adult male Wistar rats through measurement of carbon monoxide by gas chromatography. All four metalloporphyrins inhibited intestinal HO, under the light-limited conditions of these experiments. The zinc porphyrins showed a clear concentration dependency over the entire range, reducing activity to near zero levels at their highest concentrations. The tin porphyrins reduced HO activity to 26% of initial levels, but the inhibition was not clearly concentration dependent. Liver and spleen supernatants exhibited concentration dependent inhibition by all four metalloporphyrins. We also assessed the effect of light on HO activity measurements. HO determinations in the light (8 pW/cmz/nm) yielded higher HO activity than for reactions performed in the dark. The presence of light and SnPP appeared to stimulate the H O activity of intestinal preparations thus overcoming the observed inhibition. Light and SnPP also decreased to a lesser degree the inhibition for the spleen preparation, but not for the liver. We conclude that heme oxygenase activity measurements via CO determination need to be conducted in the absence of light, in particular when photosensitizers are present. Furthermore, it appears that intestinal HO behaves in a quantitatively different way from other tissues, under varying conditions of metalloporphyrin inhibition and light exposure. (Pediatr Res 26:362-365,1989) Abbreviations HO, heme oxygenase ZnPP, zinc protoporphyrin ZnMP, zinc mesoporphyrin SnPP, tin protoporphyrin SnMP, tin mesoporphyrin Jaundice, a problem common to the human neonate, results from increased bilirubin production and immaturity of the bilirubin-conjugating mechanism in the liver. HO, the rate-limiting enzyme (E.C. 1.14.99.3) in the heme catabolic pathway, cleaves
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