The Experts below are selected from a list of 231 Experts worldwide ranked by ideXlab platform
Judit Fidy - One of the best experts on this subject based on the ideXlab platform.
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Comparison of binding ability and location of two Mesoporphyrin derivatives in liposomes explored with conventional and site-selective fluorescence spectroscopy.
Biophysical Journal, 2012Co-Authors: Daniel V. Veres, Judit Fidy, István Voszka, Gabriella Csík, Barnabás Böcskei-antal, Andras D. Kaposi, Karoly Modos, Levente HerenyiAbstract:Application of porphyrins as photosensitizers is based on their light-triggered generation of reactive oxygen species (ROS) that may cause oxidative tissue damage and ultimately kill cells. Cellular membranes are the action grounds of many sensitizers due to their hydrophobic or amphiphilic character as well as the location of many of the targets attacked by ROS. Hence, the binding ability and location of porphyrins in liposomes as simple models of cellular membranes are of outstanding interest. Here we compare Mesoporphyrin IX dimethyl ester (MPE) and its nonesterified form, Mesoporphyrin IX dihydrochloride (MPCl). Monocomponent small unilamellar vesicles formed of various saturated phosphatidylcholines with incorporated Mesoporphyrins were investigated. We determined the binding parameters and the inhomogeneous distribution functions (IDFs) by different fluorescence techniques. We found in general that the binding ability of MPE is considerably greater than that of MPCl. In the case of MPCl, the IDFs suggest that only one of the two binding site types identified earlier for MPE ("site II") exists; the other one ("site I") vanishes while a new one appears ("site III"). We can confirm that "site I" is located between the two lipid layers, "site II" is situated between the hydrocarbon chains, while the location of the novel "site III" is along the outer part of the hydrocarbon chains partially inserted between the lipid head groups.
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Location of Mesoporphyrin in Liposomes Determined by Site-Selective Fluorescence Spectroscopy
The journal of physical chemistry. B, 2009Co-Authors: Levente Herenyi, István Voszka, Gabriella Csík, Daniel V. Veres, Andras D. Kaposi, Karoly Modos, Sándor Békási, Judit FidyAbstract:Binding of photosensitizers to target cells is a crucial step during the photodynamic effect. Sensitizer distribution is a good indication of whether the chemical is a good candidate for perturbing cell membrane integrity. Hence, the photophysical properties of porphyrinoid sensitizers in microheterogeneous systems such as liposomes are of outstanding interest. Here we present a site-selective fluorescence study of liposome systems. Monocomponent, small unilamellar vesicles formed of different phosphatidylcholines with incorporated Mesoporphyrin were investigated. The size distribution of liposomes was measured by dynamic light scattering after each step of the experiment. On the basis of fluorescence line narrowing spectra of Mesoporphyrin, the inhomogeneous distribution function was determined in order to characterize the photosensitizer location. The dual character of the functions revealed two different locations. Decomposition of the inhomogeneous distribution functions into Gaussians and the analysis of the fit results suggest that one of the locations for Mesoporphyrin is between the two lipid layers, and the other one is between the hydrocarbon chains of the lipid molecules.
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variety in the coupling of Mesoporphyrin ix to apohorseradish peroxidase c studied by energy selected fluorescence excitation and vibronic hole burning spectroscopy
Journal of Physical Chemistry B, 1998Co-Authors: Levente Herenyi, Judit Fidy, Koit Mauring, Katalin Kispetik, A. Suisalu, J KikasAbstract:The coupling between the heme and the surrounding protein in horseradish peroxidase was studied after substituting the iron protoheme by Mesoporphyrin IX to produce a sample measurable by high-resolution fluorescence spectroscopy. The inner ring phototautomerization of Mesoporphyrin was used to create a variety of prosthetic group configurations that were shown to be stable at cryogenic temperatures. Due to the properties of the heme crevice, some tautomeric states are characterized by distinct spectral bands. The original band of the tautomeric form stable at room temperature (B1) and two of those produced by photobleaching (B2, B3) could be selectively studied by two techniques, i.e., energy selected fluorescence excitation and vibronic hole burning spectroscopy. The line narrowed spectra were similar in the cases of complexes B2 and B3, while both are different from that of B1. From these spectra, four characteristic vibronic lines were selected and further studied by spectral hole burning experiments....
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Energy landscape of the tautomer states of Mesoporphyrin embedded in horseradish peroxidase
Biophysical journal, 1995Co-Authors: Levente Herenyi, J Gafert, Judit Fidy, Josef FriedrichAbstract:The energy hypersurface of the dominant tautomer states of Mesoporphyrin-substituted horseradish peroxidase was determined by creation of a nonequilibrium population of these states through photochemical transformation at 5 K and measurement of the temperature changes of the respective spectral bands as they were warmed to room temperature.
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correlation between protein conformation and prosthetic group configuration as tested by ph effects a hole burning study on Mesoporphyrin ix substituted horseradish peroxidase
The Journal of Physical Chemistry, 1994Co-Authors: J Gafert, Jane M. Vanderkooi, J. Friedrich, Judit FidyAbstract:The optical absorption spectrum of Mesoporphyrin-IX-substituted horseradish peroxidase shows a series of electronic origins with a typical spacing on the order of 100 cm -1 . These origins correspond with different tautomer states of Mesoporphyrin-IX. A change in the pH from 8 to 5 induces severe changes in structure as well as in the intensity distribution of the tautomer origins. In addition, the pattern of photochemical tautomer transformation changes significantly. The straightforward interpretation is that a change in pH leads to a structural accommodation of the apoprotein. This structural rearrangement influences the energy hypersurface of the prosthetic group leading to the change in the origin spectrum observed
Levente Herenyi - One of the best experts on this subject based on the ideXlab platform.
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Comparison of binding ability and location of two Mesoporphyrin derivatives in liposomes explored with conventional and site-selective fluorescence spectroscopy.
Biophysical Journal, 2012Co-Authors: Daniel V. Veres, Judit Fidy, István Voszka, Gabriella Csík, Barnabás Böcskei-antal, Andras D. Kaposi, Karoly Modos, Levente HerenyiAbstract:Application of porphyrins as photosensitizers is based on their light-triggered generation of reactive oxygen species (ROS) that may cause oxidative tissue damage and ultimately kill cells. Cellular membranes are the action grounds of many sensitizers due to their hydrophobic or amphiphilic character as well as the location of many of the targets attacked by ROS. Hence, the binding ability and location of porphyrins in liposomes as simple models of cellular membranes are of outstanding interest. Here we compare Mesoporphyrin IX dimethyl ester (MPE) and its nonesterified form, Mesoporphyrin IX dihydrochloride (MPCl). Monocomponent small unilamellar vesicles formed of various saturated phosphatidylcholines with incorporated Mesoporphyrins were investigated. We determined the binding parameters and the inhomogeneous distribution functions (IDFs) by different fluorescence techniques. We found in general that the binding ability of MPE is considerably greater than that of MPCl. In the case of MPCl, the IDFs suggest that only one of the two binding site types identified earlier for MPE ("site II") exists; the other one ("site I") vanishes while a new one appears ("site III"). We can confirm that "site I" is located between the two lipid layers, "site II" is situated between the hydrocarbon chains, while the location of the novel "site III" is along the outer part of the hydrocarbon chains partially inserted between the lipid head groups.
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Location of Mesoporphyrin in Liposomes Determined by Site-Selective Fluorescence Spectroscopy
The journal of physical chemistry. B, 2009Co-Authors: Levente Herenyi, István Voszka, Gabriella Csík, Daniel V. Veres, Andras D. Kaposi, Karoly Modos, Sándor Békási, Judit FidyAbstract:Binding of photosensitizers to target cells is a crucial step during the photodynamic effect. Sensitizer distribution is a good indication of whether the chemical is a good candidate for perturbing cell membrane integrity. Hence, the photophysical properties of porphyrinoid sensitizers in microheterogeneous systems such as liposomes are of outstanding interest. Here we present a site-selective fluorescence study of liposome systems. Monocomponent, small unilamellar vesicles formed of different phosphatidylcholines with incorporated Mesoporphyrin were investigated. The size distribution of liposomes was measured by dynamic light scattering after each step of the experiment. On the basis of fluorescence line narrowing spectra of Mesoporphyrin, the inhomogeneous distribution function was determined in order to characterize the photosensitizer location. The dual character of the functions revealed two different locations. Decomposition of the inhomogeneous distribution functions into Gaussians and the analysis of the fit results suggest that one of the locations for Mesoporphyrin is between the two lipid layers, and the other one is between the hydrocarbon chains of the lipid molecules.
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variety in the coupling of Mesoporphyrin ix to apohorseradish peroxidase c studied by energy selected fluorescence excitation and vibronic hole burning spectroscopy
Journal of Physical Chemistry B, 1998Co-Authors: Levente Herenyi, Judit Fidy, Koit Mauring, Katalin Kispetik, A. Suisalu, J KikasAbstract:The coupling between the heme and the surrounding protein in horseradish peroxidase was studied after substituting the iron protoheme by Mesoporphyrin IX to produce a sample measurable by high-resolution fluorescence spectroscopy. The inner ring phototautomerization of Mesoporphyrin was used to create a variety of prosthetic group configurations that were shown to be stable at cryogenic temperatures. Due to the properties of the heme crevice, some tautomeric states are characterized by distinct spectral bands. The original band of the tautomeric form stable at room temperature (B1) and two of those produced by photobleaching (B2, B3) could be selectively studied by two techniques, i.e., energy selected fluorescence excitation and vibronic hole burning spectroscopy. The line narrowed spectra were similar in the cases of complexes B2 and B3, while both are different from that of B1. From these spectra, four characteristic vibronic lines were selected and further studied by spectral hole burning experiments....
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Energy landscape of the tautomer states of Mesoporphyrin embedded in horseradish peroxidase
Biophysical journal, 1995Co-Authors: Levente Herenyi, J Gafert, Judit Fidy, Josef FriedrichAbstract:The energy hypersurface of the dominant tautomer states of Mesoporphyrin-substituted horseradish peroxidase was determined by creation of a nonequilibrium population of these states through photochemical transformation at 5 K and measurement of the temperature changes of the respective spectral bands as they were warmed to room temperature.
Attallah Kappas - One of the best experts on this subject based on the ideXlab platform.
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Comparative pharmacology of zinc Mesoporphyrin and tin Mesoporphyrin: toxic actions of zinc Mesoporphyrin on hematopoiesis and progenitor cell mobilization.
Pharmacology, 1999Co-Authors: J.d. Lutton, George S. Drummond, S. Jiang, Nader G. Abraham, Attallah KappasAbstract:The effects of two synthetic heme analogues, zinc Mesoporphyrin (ZnMP) and tin Mesoporphyrin (SnMP), on in vivo hematopoietic progenitor cell mobilization and in vitro hematopoiesis were examined in rabbit bone marrow. Rabbits received granulocyte colony-stimulating factor (rhG-CSF) for 7 days in order to mobilize increased numbers of erythroid (BFU-E) and myeloid (CFU-GM) progenitors in peripheral blood. Concurrent treatment of rhG-CSF-treated rabbits with ZnMP reduced mobilization of the numbers of BFU-E (76% inhibition, p < 0.0001) and CFU-GM (70% inhibition, p < 0.005) in peripheral blood. In contrast, SnMP administered at the same concentration had no significant suppressive effect on BFU-E and CFU-GM recruitment. Both metalloporphyrins inhibited bone marrow heme oxygenase activity equally in vivo, thus indicating that both compounds enter bone marrow cells. Direct in vitro addition of ZnMP to normal rabbit bone marrow cultures suppressed BFU-E and CFU-GM growth, whereas SnMP had no such effect. These results confirm, in an in vivo system, our earlier in vitro studies and demonstrate that, at the concentrations studied, ZnMP, in contrast to SnMP, displays toxicity for hematopoietic growth and progenitor cell production.
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Tissue distribution of synthetic heme analogues: studies with tin, chromium, and zinc Mesoporphyrins.
Pharmacology, 1996Co-Authors: Elisabeth A. Bundock, George S. Drummond, Attallah KappasAbstract:The uptake in tissue of Sn-Mesoporphyrin (SnMP), Cr-Mesoporphyrin (CrMP) and Zn-Mesoporphyrin (ZnMP) administered at doses ranging from 1 to 10 µmol/kg BW and the effects of these compounds on heme oxygenase activity were examined in both adult and neonatal rats. SnMP and CrMP, but not ZnMP, were rapidly cleared from blood and taken up by liver, spleen and kidney where marked inhibition of heme oxygenase activity was demonstrated. None of the metalloporphyrins were detectable in brain, and no inhibition of heme oxygenase activity was demonstrable in this tissue after administration of the compounds to both adult and neonatal rats. These results demonstrate that SnMP, CrMP and ZnMP do not cross the blood brain barrier, a fact of interest in relation to the potential use of these compounds clinically.
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Tin-Mesoporphyrin Inhibits Heme Oxygenase Activity and Heme-Iron Absorption in the Intestine
Pharmacology, 1993Co-Authors: Roland E. Böni, George S. Drummond, Richard A. Galbraith, Rahel A. Huch Böni, Attallah KappasAbstract:Long-term treatment with the heme oxygenase inhibitor tin-Mesoporphyrin produces an iron deficiency anemia in rats analogous to that we reported in patients with the Crigler-Najjar type I syndrome receiving prolonged treatment with the inhibitor to ameliorate severe jaundice [Pediatrics 1992; 89: 175-182]. A dose- and time-dependent inhibition of intestinal heme oxygenase is produced by tin-Mesoporphyrin which is independent of iron status of the animal. Tin-Mesoporphyrin inhibits the intestinal enzyme whether administered orally or parenterally. Enzyme inhibition by either route results in diminished uptake of 59Fe from radiolabelled heme in the gut. Since tin-Mesoporphyrin stimulates excretion of unmetabolized heme into bile its ability to inhibit intestinal heme oxygenase and to decrease heme-iron absorption in the gut probably accounts in part for the iron deficiency produced by the agent. The availability of an orally active agent which inhibits heme oxygenase and heme-iron absorption in the intestine may prove useful for experimental and therapeutic studies in diseases of iron metabolism.
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Intestinal heme oxygenase inhibition and increased biliary iron excretion by metalloporphyrins.
Gastroenterology, 1992Co-Authors: George S. Drummond, D. W. Von Rosenberg, Attallah KappasAbstract:The effects of synthetic metalloporphyrins on heme oxygenase activity in the epithelium of the proximal region of the small intestine were examined both in vitro and in vivo in male Sprague-Dawley rats. Metalloporphyrins, which inhibit hepatic heme oxygenase in vitro, also inhibit intestinal heme oxygenase. Chromium and tin porphyrins are the most potent inhibitors of the intestinal enzyme in vitro. Oral administration of Sn-protoporphyrin (25 mumol/kg body weight) resulted in inhibition of intestinal heme oxygenase; however, no effect was observed on the splenic, hepatic, or renal enzymes. Metal analyses in these tissues showed essentially no intestinal absorption of the metalloporphyrin. Oral administration of Cr-Mesoporphyrin (25 mumol/kg body wt) also resulted in inhibition of intestinal heme oxygenase activity. Zinc and manganese Mesoporphyrin did not inhibit intestinal heme oxygenase activity when administered orally. Microsomal intestinal heme oxygenase activity was inhibited in a dose-dependent manner by antiserum raised in rabbit against rat hepatic heme oxygenase. The parenteral administration of metalloporphyrin inhibitors of heme oxygenase to bile duct-cannulated rats resulted in a significant increase in iron levels in the bile.
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Comparative photoactivity of tin and zinc porphyrin inhibitors of heme oxygenase: pronounced photolability of the zinc compounds.
Photochemistry and photobiology, 1991Co-Authors: Nancy L. Greenbaum, Attallah KappasAbstract:Metalloporphyrin inhibitors of heme oxygenase may also have photosensitizing properties in vivo. To assess photoactivity in serum, the relative ability to mediate photooxidation of tryptophan or other oxidizable targets, presumably by singlet oxygen production, was measured for tin Mesoporphyrin, zinc Mesoporphyrin, and zinc deuteroporphyrin bisglycol in aqueous solution and when bound to human serum albumin. While tin Mesoporphyrin sensitized at the greatest initial rate in aqueous solution, the zinc compounds sensitized at a greater initial rate in detergent micelles or when bound to albumin. There was minimal alteration of the tin Mesoporphyrin during the time course of illumination in the Soret or visible absorption regions. The zinc compounds, however, proved to be extremely photolabile and were extensively destroyed by light; the photooxidized forms were found to be ineffective as inhibitors of heme oxygenase.
Daniel V. Veres - One of the best experts on this subject based on the ideXlab platform.
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Comparison of binding ability and location of two Mesoporphyrin derivatives in liposomes explored with conventional and site-selective fluorescence spectroscopy.
Biophysical Journal, 2012Co-Authors: Daniel V. Veres, Judit Fidy, István Voszka, Gabriella Csík, Barnabás Böcskei-antal, Andras D. Kaposi, Karoly Modos, Levente HerenyiAbstract:Application of porphyrins as photosensitizers is based on their light-triggered generation of reactive oxygen species (ROS) that may cause oxidative tissue damage and ultimately kill cells. Cellular membranes are the action grounds of many sensitizers due to their hydrophobic or amphiphilic character as well as the location of many of the targets attacked by ROS. Hence, the binding ability and location of porphyrins in liposomes as simple models of cellular membranes are of outstanding interest. Here we compare Mesoporphyrin IX dimethyl ester (MPE) and its nonesterified form, Mesoporphyrin IX dihydrochloride (MPCl). Monocomponent small unilamellar vesicles formed of various saturated phosphatidylcholines with incorporated Mesoporphyrins were investigated. We determined the binding parameters and the inhomogeneous distribution functions (IDFs) by different fluorescence techniques. We found in general that the binding ability of MPE is considerably greater than that of MPCl. In the case of MPCl, the IDFs suggest that only one of the two binding site types identified earlier for MPE ("site II") exists; the other one ("site I") vanishes while a new one appears ("site III"). We can confirm that "site I" is located between the two lipid layers, "site II" is situated between the hydrocarbon chains, while the location of the novel "site III" is along the outer part of the hydrocarbon chains partially inserted between the lipid head groups.
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Location of Mesoporphyrin in Liposomes Determined by Site-Selective Fluorescence Spectroscopy
The journal of physical chemistry. B, 2009Co-Authors: Levente Herenyi, István Voszka, Gabriella Csík, Daniel V. Veres, Andras D. Kaposi, Karoly Modos, Sándor Békási, Judit FidyAbstract:Binding of photosensitizers to target cells is a crucial step during the photodynamic effect. Sensitizer distribution is a good indication of whether the chemical is a good candidate for perturbing cell membrane integrity. Hence, the photophysical properties of porphyrinoid sensitizers in microheterogeneous systems such as liposomes are of outstanding interest. Here we present a site-selective fluorescence study of liposome systems. Monocomponent, small unilamellar vesicles formed of different phosphatidylcholines with incorporated Mesoporphyrin were investigated. The size distribution of liposomes was measured by dynamic light scattering after each step of the experiment. On the basis of fluorescence line narrowing spectra of Mesoporphyrin, the inhomogeneous distribution function was determined in order to characterize the photosensitizer location. The dual character of the functions revealed two different locations. Decomposition of the inhomogeneous distribution functions into Gaussians and the analysis of the fit results suggest that one of the locations for Mesoporphyrin is between the two lipid layers, and the other one is between the hydrocarbon chains of the lipid molecules.
George S. Drummond - One of the best experts on this subject based on the ideXlab platform.
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Chemoprevention of severe neonatal hyperbilirubinemia.
Seminars in Perinatology, 2004Co-Authors: George S. DrummondAbstract:The uses of synthetic heme analogues that are competitive inhibitors of heme oxygenase, the rate-limiting enzyme in the production of bilirubin, represent a novel means of controlling severe hyperbilirubinemia in the newborn. The logic of this approach and the use of stannsoporfin (tin Mesoporphyrin) as the compound of choice are discussed.
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Comparative pharmacology of zinc Mesoporphyrin and tin Mesoporphyrin: toxic actions of zinc Mesoporphyrin on hematopoiesis and progenitor cell mobilization.
Pharmacology, 1999Co-Authors: J.d. Lutton, George S. Drummond, S. Jiang, Nader G. Abraham, Attallah KappasAbstract:The effects of two synthetic heme analogues, zinc Mesoporphyrin (ZnMP) and tin Mesoporphyrin (SnMP), on in vivo hematopoietic progenitor cell mobilization and in vitro hematopoiesis were examined in rabbit bone marrow. Rabbits received granulocyte colony-stimulating factor (rhG-CSF) for 7 days in order to mobilize increased numbers of erythroid (BFU-E) and myeloid (CFU-GM) progenitors in peripheral blood. Concurrent treatment of rhG-CSF-treated rabbits with ZnMP reduced mobilization of the numbers of BFU-E (76% inhibition, p < 0.0001) and CFU-GM (70% inhibition, p < 0.005) in peripheral blood. In contrast, SnMP administered at the same concentration had no significant suppressive effect on BFU-E and CFU-GM recruitment. Both metalloporphyrins inhibited bone marrow heme oxygenase activity equally in vivo, thus indicating that both compounds enter bone marrow cells. Direct in vitro addition of ZnMP to normal rabbit bone marrow cultures suppressed BFU-E and CFU-GM growth, whereas SnMP had no such effect. These results confirm, in an in vivo system, our earlier in vitro studies and demonstrate that, at the concentrations studied, ZnMP, in contrast to SnMP, displays toxicity for hematopoietic growth and progenitor cell production.
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Tissue distribution of synthetic heme analogues: studies with tin, chromium, and zinc Mesoporphyrins.
Pharmacology, 1996Co-Authors: Elisabeth A. Bundock, George S. Drummond, Attallah KappasAbstract:The uptake in tissue of Sn-Mesoporphyrin (SnMP), Cr-Mesoporphyrin (CrMP) and Zn-Mesoporphyrin (ZnMP) administered at doses ranging from 1 to 10 µmol/kg BW and the effects of these compounds on heme oxygenase activity were examined in both adult and neonatal rats. SnMP and CrMP, but not ZnMP, were rapidly cleared from blood and taken up by liver, spleen and kidney where marked inhibition of heme oxygenase activity was demonstrated. None of the metalloporphyrins were detectable in brain, and no inhibition of heme oxygenase activity was demonstrable in this tissue after administration of the compounds to both adult and neonatal rats. These results demonstrate that SnMP, CrMP and ZnMP do not cross the blood brain barrier, a fact of interest in relation to the potential use of these compounds clinically.
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Tin-Mesoporphyrin Inhibits Heme Oxygenase Activity and Heme-Iron Absorption in the Intestine
Pharmacology, 1993Co-Authors: Roland E. Böni, George S. Drummond, Richard A. Galbraith, Rahel A. Huch Böni, Attallah KappasAbstract:Long-term treatment with the heme oxygenase inhibitor tin-Mesoporphyrin produces an iron deficiency anemia in rats analogous to that we reported in patients with the Crigler-Najjar type I syndrome receiving prolonged treatment with the inhibitor to ameliorate severe jaundice [Pediatrics 1992; 89: 175-182]. A dose- and time-dependent inhibition of intestinal heme oxygenase is produced by tin-Mesoporphyrin which is independent of iron status of the animal. Tin-Mesoporphyrin inhibits the intestinal enzyme whether administered orally or parenterally. Enzyme inhibition by either route results in diminished uptake of 59Fe from radiolabelled heme in the gut. Since tin-Mesoporphyrin stimulates excretion of unmetabolized heme into bile its ability to inhibit intestinal heme oxygenase and to decrease heme-iron absorption in the gut probably accounts in part for the iron deficiency produced by the agent. The availability of an orally active agent which inhibits heme oxygenase and heme-iron absorption in the intestine may prove useful for experimental and therapeutic studies in diseases of iron metabolism.
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Intestinal heme oxygenase inhibition and increased biliary iron excretion by metalloporphyrins.
Gastroenterology, 1992Co-Authors: George S. Drummond, D. W. Von Rosenberg, Attallah KappasAbstract:The effects of synthetic metalloporphyrins on heme oxygenase activity in the epithelium of the proximal region of the small intestine were examined both in vitro and in vivo in male Sprague-Dawley rats. Metalloporphyrins, which inhibit hepatic heme oxygenase in vitro, also inhibit intestinal heme oxygenase. Chromium and tin porphyrins are the most potent inhibitors of the intestinal enzyme in vitro. Oral administration of Sn-protoporphyrin (25 mumol/kg body weight) resulted in inhibition of intestinal heme oxygenase; however, no effect was observed on the splenic, hepatic, or renal enzymes. Metal analyses in these tissues showed essentially no intestinal absorption of the metalloporphyrin. Oral administration of Cr-Mesoporphyrin (25 mumol/kg body wt) also resulted in inhibition of intestinal heme oxygenase activity. Zinc and manganese Mesoporphyrin did not inhibit intestinal heme oxygenase activity when administered orally. Microsomal intestinal heme oxygenase activity was inhibited in a dose-dependent manner by antiserum raised in rabbit against rat hepatic heme oxygenase. The parenteral administration of metalloporphyrin inhibitors of heme oxygenase to bile duct-cannulated rats resulted in a significant increase in iron levels in the bile.