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Suppression of Carbon Monoxide Excretion Rate by Tin Protoporphyrin FREE

Andrew M. Posselt; Linda K. Kwong, PhD; Hendrik J. Vreman, PhD; David K. Stevenson, MD
[+] Author Affiliations

Accepted for publication Oct 3, 1985.

Reprint requests to Department of Pediatrics, S222, Stanford University School of Medicine, Stanford, CA 94305 (Dr Stevenson).


Am J Dis Child. 1986;140(2):147-150. doi:10.1001/archpedi.1986.02140160065034.
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• The effect of a single prophylactic dose of tin protoporphyrin on the carbon monoxide (CO) excretion rate of antibiotic-treated neonatal rats before and after hematoma formation was evaluated. The CO excretion rate, reflecting the rate of bilirubin production, of tin protoporphyrin-treated (TP-H) rats 24 hours after injection of 65 mole of tin protoporphyrin per kilogram (time [t] = 0 hours) was approximately 18% lower than those of the saline-control (S-C) and saline-hematoma (S-H) rats, but this difference was no longer evident at t=43 hours. After hematoma formation at t=44 hours, the CO excretion rate of the S-H rats increased rapidly; this increase was delayed and lessened in the TP-H rats. At eight hours posthematoma (t = 52 hours), the CO excretion rate of the TP-H rats was significantly lower than that of the S-H rats, 53±2 vs 73±3 μL/kg/hr, respectively. A maximal rate of 89±5 μL/kg/hr was reached 25 hours posthematoma in the S-H rats (t= 69 hours), as compared with 80±3 μL/kg/hr at 44 hours posthematoma in the TP-H rats (t= 88 hours). The recovery of injected blood as CO over a 68-hour study period was approximately 90% for the S-H rats and approximately 65% for the TP-H rats. At t=112 hours, hepatic heme oxygenase activity of the TP-H rats was still significantly lower than that of the S-H and S-C rats; however, plasma bilirubin concentrations of all three groups were similar. These studies demonstrate that tin protoporphyrin is an effective in vivo inhibitor of endogenous heme catabolism as measured by the CO excretion rate in antibiotic-treated neonatal rats with and without artificially created hematomas.

(AJDC 1986;140:147-150)

REFERENCES

Drummond GS, Kappas A:  Prevention of neonatal hyperbilirubinemia by tin protoporphyrin IX, a potent competitive inhibitor of heme oxidation . Proc Natl Acad Sci USA 1981;;78: 6466-6470.
Drummond GS, Kappas A:  Chemoprevention of neonatal jaundice: Potency of tin-protoporphyrin in an animal model . Science 1982;;217: 1250-1252.
Drummond GS, Kappas A:  An experimental model of postnatal jaundice in the suckling rat: Suppression of induced-hyperbilirubinemia by Sn-protoporphyrin . J Clin Invest 1984;;74: 142-149.
Kappas A, Drummond GS, Simionatto CS, et al:  Control of heme oxygenase and plasma levels of bilirubin by a synthetic heme analogue, tin-protoporphyrin . Hepatology 1984;;4:336-341.
Sassa S, Drummond GS, Bernstein SE, et al:  Tin-protoporphyrin suppression of hyperbilirubinemia in mutant mice with severe hemolytic anemia . Blood 1983;;61:1011-1013.
Cornelius CE, Rodgers PA:  Prevention of neonatal hyperbilirubinemia in Rhesus monkeys by tin protoporphyrin . Pediatr Res 1984;;18: 728-738.
Stevenson DK, Ostrander CR, Cohen RS, et al:  Trace gas analysis in bilirubin metabolism: A technical review and current state of the art . Adv Pediatr 1982;;29:129-149.
Cowan BE, Kwong LK, Vreman HJ, et al:  The effect of tin protoporphyrin on the bilirubin production rate in newborn rats . Pediatr Pharmacol 1983;;3:95-100.
Posselt AM, Cowan BE, Kwong LK, et al: Effect of tin protoporphyrin on the excretion rate of carbon monoxide in newborn rats after hematoma formation. J Pediatr Gastroenterol Nutr, in press.
Milleville GS, Levitt MD, Engel RR:  Tin protoporphyrin inhibits carbon monoxide production in adult mice . Pediatr Res 1985;;17:94-96.
Petryka ZJ, Pierach CA, Smich A, et al:  Biliary excretion of exogenous hematin in rats . Life Sci 1977;;21:1015-1020.
McCormack LR, Liem HH, Strum WB, et al:  Effects of haem infusion on biliary secretion of porphyrine, haem and bilirubin in man . Eur J Clin Invest 1982;;12:257-262.
Kappas A, Simionatto CS, Drummond GS, et al:  The liver excretes large amounts of heme into bile when heme oxygenase is inhibited competitively by Sn-protoporphyrin . Proc Natl Acad Sci USA 1985;;82:896-900.
Engel RR, Matsen JM, Chapman SS, et al:  Carbon monoxide production from heme compounds by bacteria . J Bacteriol 1972;;112: 1310-1315.
Stevenson DK, Ostrander CR, Johnson JD:  Effect of erythrocyte destruction on the pulmonary excretion rate of carbon monoxide in adult male Wistar rats . J Lab Clin Med 1979;;94: 649-654.
Tenhunen R, Marver HS, Schmid R:  The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase . Proc Natl Acad Sci USA 1968;;61:748-755.
Lowry OH, Rosenborough HJ, Fan AL, et al:  Protein measurement with the Folin phenol reagent . J Biol Chem 1951;;193:265-275.
Maines MD, Cohn J:  Bile pigment formation by skin heme oxygenase: Studies on the response of the enzyme to heme compounds and tissue injury . J Exp Med 1977;;145:1054-1059.
Anderson KE, Simionatto CS, Drummond GS, et al:  Tissue distribution and disposition of tin-protoporphyrin, a potent competitive inhibitor of heme oxygenase . J Pharmacol Exp Ther 1984;;228:327-333.

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References

Drummond GS, Kappas A:  Prevention of neonatal hyperbilirubinemia by tin protoporphyrin IX, a potent competitive inhibitor of heme oxidation . Proc Natl Acad Sci USA 1981;;78: 6466-6470.
Drummond GS, Kappas A:  Chemoprevention of neonatal jaundice: Potency of tin-protoporphyrin in an animal model . Science 1982;;217: 1250-1252.
Drummond GS, Kappas A:  An experimental model of postnatal jaundice in the suckling rat: Suppression of induced-hyperbilirubinemia by Sn-protoporphyrin . J Clin Invest 1984;;74: 142-149.
Kappas A, Drummond GS, Simionatto CS, et al:  Control of heme oxygenase and plasma levels of bilirubin by a synthetic heme analogue, tin-protoporphyrin . Hepatology 1984;;4:336-341.
Sassa S, Drummond GS, Bernstein SE, et al:  Tin-protoporphyrin suppression of hyperbilirubinemia in mutant mice with severe hemolytic anemia . Blood 1983;;61:1011-1013.
Cornelius CE, Rodgers PA:  Prevention of neonatal hyperbilirubinemia in Rhesus monkeys by tin protoporphyrin . Pediatr Res 1984;;18: 728-738.
Stevenson DK, Ostrander CR, Cohen RS, et al:  Trace gas analysis in bilirubin metabolism: A technical review and current state of the art . Adv Pediatr 1982;;29:129-149.
Cowan BE, Kwong LK, Vreman HJ, et al:  The effect of tin protoporphyrin on the bilirubin production rate in newborn rats . Pediatr Pharmacol 1983;;3:95-100.
Posselt AM, Cowan BE, Kwong LK, et al: Effect of tin protoporphyrin on the excretion rate of carbon monoxide in newborn rats after hematoma formation. J Pediatr Gastroenterol Nutr, in press.
Milleville GS, Levitt MD, Engel RR:  Tin protoporphyrin inhibits carbon monoxide production in adult mice . Pediatr Res 1985;;17:94-96.
Petryka ZJ, Pierach CA, Smich A, et al:  Biliary excretion of exogenous hematin in rats . Life Sci 1977;;21:1015-1020.
McCormack LR, Liem HH, Strum WB, et al:  Effects of haem infusion on biliary secretion of porphyrine, haem and bilirubin in man . Eur J Clin Invest 1982;;12:257-262.
Kappas A, Simionatto CS, Drummond GS, et al:  The liver excretes large amounts of heme into bile when heme oxygenase is inhibited competitively by Sn-protoporphyrin . Proc Natl Acad Sci USA 1985;;82:896-900.
Engel RR, Matsen JM, Chapman SS, et al:  Carbon monoxide production from heme compounds by bacteria . J Bacteriol 1972;;112: 1310-1315.
Stevenson DK, Ostrander CR, Johnson JD:  Effect of erythrocyte destruction on the pulmonary excretion rate of carbon monoxide in adult male Wistar rats . J Lab Clin Med 1979;;94: 649-654.
Tenhunen R, Marver HS, Schmid R:  The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase . Proc Natl Acad Sci USA 1968;;61:748-755.
Lowry OH, Rosenborough HJ, Fan AL, et al:  Protein measurement with the Folin phenol reagent . J Biol Chem 1951;;193:265-275.
Maines MD, Cohn J:  Bile pigment formation by skin heme oxygenase: Studies on the response of the enzyme to heme compounds and tissue injury . J Exp Med 1977;;145:1054-1059.
Anderson KE, Simionatto CS, Drummond GS, et al:  Tissue distribution and disposition of tin-protoporphyrin, a potent competitive inhibitor of heme oxygenase . J Pharmacol Exp Ther 1984;;228:327-333.

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