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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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Electric field and conformational effects in cytochrome c peroxidase studied by high-resolution fluorescence spectroscopy and electrostatic calculations
Time-Resolved Laser Spectroscopy in Biochemistry IV, 1994Co-Authors: Jane M. Vanderkooi, Judit Fidy, Takashi Yonetani, Kim A. Sharp, Helen AnniAbstract:Mesoporphyrin IX was used as a fluorescent analogue of heme in cytochrome c peroxidase (CcP). Details of the fluorescence spectra of CcP obtained under conditions of energy selection revealed interactions of the porphyrin with the heme pocket. It was shown that the energy of a 0,0 transition shifted with pH in parallel with changes in the electric field of the protein.
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.
Tae-hwan Lim - One of the best experts on this subject based on the ideXlab platform.
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occlusive myocardial infarction investigation of bis gadolinium Mesoporphyrins enhanced t1 weighted mr imaging in a cat model
Radiology, 2001Co-Authors: Seong Hoon Choi, Seung Soo Lee, Sang Il Choi, Sang Tae Kim, Keun Ho Lim, Chung Hwan Lim, Hanns-joachim Weinmann, Tae-hwan LimAbstract:PURPOSE: To test whether bis-gadolinium Mesoporphyrins–enhanced magnetic resonance (MR) imaging can accurately depict irreversibly damaged myocardium in occlusive myocardial infarction. MATERIALS AND METHODS: Ten cats were subjected to 90 minutes of occlusion of the left anterior descending coronary artery. Bis-gadolinium Mesoporphyrins–enhanced T1-weighted MR imaging was performed in the cats for 6 hours. Histopathologic examinations with 2’3’5-triphenyl tetrazolium chloride (TTC) staining and electron microscopy were performed on the resected specimens. The time course and pattern of signal intensity enhancement were evaluated. The size of the infarcted myocardium was estimated on the MR images by measuring the size of the signal intensity–enhanced area. RESULTS: In eight of 10 cats, it was impossible to distinguish infarcted myocardium from normal myocardium at visual inspection of T1-weighted MR images. The contrast ratio between infarcted and normal myocardium did not increase significantly over time...
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Occlusive Myocardial Infarction: Investigation of Bis-Gadolinium Mesoporphyrins–enhanced T1-weighted MR Imaging in a Cat Model
Radiology, 2001Co-Authors: Seong Hoon Choi, Seung Soo Lee, Sang Il Choi, Sang Tae Kim, Keun Ho Lim, Chung Hwan Lim, Hanns-joachim Weinmann, Tae-hwan LimAbstract:PURPOSE: To test whether bis-gadolinium Mesoporphyrins–enhanced magnetic resonance (MR) imaging can accurately depict irreversibly damaged myocardium in occlusive myocardial infarction. MATERIALS AND METHODS: Ten cats were subjected to 90 minutes of occlusion of the left anterior descending coronary artery. Bis-gadolinium Mesoporphyrins–enhanced T1-weighted MR imaging was performed in the cats for 6 hours. Histopathologic examinations with 2’3’5-triphenyl tetrazolium chloride (TTC) staining and electron microscopy were performed on the resected specimens. The time course and pattern of signal intensity enhancement were evaluated. The size of the infarcted myocardium was estimated on the MR images by measuring the size of the signal intensity–enhanced area. RESULTS: In eight of 10 cats, it was impossible to distinguish infarcted myocardium from normal myocardium at visual inspection of T1-weighted MR images. The contrast ratio between infarcted and normal myocardium did not increase significantly over time...
Udo P Schmiedl - One of the best experts on this subject based on the ideXlab platform.
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Intestinal absorption of Mn-mesoporphyrin in a small bowel sac system: Effect of oleic acid
Academic radiology, 1997Co-Authors: Gabriele Von Ingersleben, James A. Nelson, Udo P Schmiedl, Penny Dong, Frank StarrAbstract:Rationale and Objectives. The authors investigated the effect of oleic acid (cis-9-octadecenoic acid) (OA), a lipidic carrier, on the intestinal absorption rate and T1 relaxation time of manganese (III) mesoporphyrin (Mn-mesoporphyrin), a prototype hepatobiliary contrast agent for magnetic resonance imaging. Methods. Mn-mesoporphyrin was formulated with OA at various concentrations. Small bowel sacs were created in 36 rats and fdled with complexed and free Mn-mesoporphyrin. Intestinal absorption of Mn-mesoporphyrin was measured with spectrophotometry at 364 nm. T1 relaxation times were measured in samples of Mn-mesoporphyrin solutions, bowel wall, liver, and bile. Results. Absorption rates ranged from 4.2%/cm2/h to 13%/cm2/h. Absorption was greatest (13%/cm2/h) when a combination of 1 mmol/L Mnmesoporphyrin and 26.5 mmol/L OA was used. The T1 of bile decreased from 2,480 to 248 msec (maximum decrease) in rats that received Mnmesoporphyrin. Conclusion. Mn-mesoporphyrin is absorbed from the small bowel in both the lipid-associated and free form, resulting in substantial shortening of the T1 in bile.
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magnetic resonance imaging of the hepatobiliary system intestinal absorption studies of manganese mesoporphyrin
Academic Radiology, 1995Co-Authors: Udo P Schmiedl, James A. Nelson, Reza Malek, Frank Starr, Linnar Teng, Rodney J Y HoAbstract:Rationale and Objectives. We studied the intestinal absorption of manganese mesoporphyrin (Mn-mesoporphyrin), a potential oral hepatobiliary contrast agent. Methods. Mn-mesoporphyrin was complexed with monoolein and taurocholate (mixed micelles). Portal venous delivery and biliary excretion were measured after intestinal administration in rats and rabbits, and the mechanism of intestinal transport was studied in a combined lymph-bile fistula model in rats. T1-weighted magnetic resonance (MR) images of the liver were obtained in rats and domestic pigs before and after gastric administration of Mn-mesoporphyrin in mixed micelles. Results. A 2.2-fold increase of portal venous Mn concentration was found 90 min after intestinal administration of the complex. None was found in the lymph collected from the thoracic duct, indicating a transcellular transport mechanism through the intestinal mucosa with portal venous delivery. Mn-mesoporphyrin levels in bile peaked between 240 and 270 min after administration (200-fold increase). The greatest liver enhancement (20–90%) was measured 360 min after administration. Conclusion. The feasibility of intestinal delivery of Mn-mesoporphyrin, a lipophilic hepatobiliary contrast agent, was demonstrated.
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Intravenous manganese-mesoporphyrin as a magnetic resonance imaging contrast agent: An experimental model using VX-2 carcinoma in rabbits
Academic radiology, 1995Co-Authors: David H. Robinson, James A. Nelson, Udo P Schmiedl, Frank L. Starr, Reza MalekAbstract:Rationale and Objectives. We investigated the potential of manganese (III) mesoporphyrin (Mn-mesoporphyrin) as a hepatobiliary contrast agent for magnetic resonance (MR) imaging in rabbits given VX-2 carcinoma liver implants. Methods. Rabbits given VX-2 carcinoma liver implants (n = 8) were imaged before and after the intravenous (IV) administration of 0.04 mmol/kg Mn-mesoporphyrin. MR images were correlated with gross-specimen cross-sections. The distribution of Mn in various tissues following IV administration of 0.04 mmol/kg Mn-mesoporphyrin was determined using atomic absorption analysis. A standard panel of serum chemistries was followed over 7 days in six rabbits following this same dose of Mn-mesoporphyrin and compared with chemistries from two control rabbits. Results. IV administration of 0.04 mmol/kg (25 mg/kg) Mn-mesoporphyrin resulted in improvement of tumor-to-liver contrast, with enhancement of normal liver (99.7 ± 14.7%) and the gallbladder (442 ± 116%), but not VX-2 tumor tissue (14.8 ± 13.9%), (n = 8, p = .05). Analysis of tissue Mn levels 100 min after IV Mn-mesoporphyrin injection demonstrated preferential distribution of Mn to normal liver tissue (57.8 ± 15.3 μg Mn/g) compared with VX-2 tumor (4.28 ± 1.48 μg Mn/g). No significant change was found in the serum chemistries of six normal rabbits over a 7-day period after the IV administration of 0.04 mmol/kg Mn-mesoporphyrin. Conclusion. IV Mn-mesoporphyrin improved lesion-to-liver contrast because of preferential distribution of Mn mesoporphyrin to normal liver parenchyma and bile.
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methods and compositions for the enteral administration of hepatobiliary mri contrast agents
Magnetic Resonance Imaging, 1993Co-Authors: James A. Nelson, Linnar L Teng, Udo P Schmiedl, Jerry C BommerAbstract:Hepatobiliary magnetic resonance imaging of a human or animal subject is enhanced by enterally administering to the subject an effective amount of a lipophilic contrast enhancing agent. Representative contrast enhancing agents include manganese mesoporphyrin, manganese deuteroporphyrin, manganese pheophorbide and manganese pyrophenophoribide, and, when administered orally, an enteric delivery agent.
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Pharmaceutical properties, biodistribution, and imaging characteristics of manganese-mesoporphyrin. A potential hepatobiliary contrast agent for magnetic resonance imaging.
Investigative radiology, 1993Co-Authors: Udo P Schmiedl, James A. Nelson, David H. Robinson, Frank L. Starr, Arne Michalson, Thomas Frenzel, Wolfgang Ebert, Gabriele Schuhmann-giampieriAbstract:OBJECTIVES Manganese (III) mesoporphyrin (Mn-mesoporphyrin) was investigated for its pharmaceutical properties and magnetic resonance imaging characteristics as a potential hepatobiliary contrast agent. METHODS Solubility, partition coefficient, plasma binding, proton relaxation enhancement, biodistribution, biliary excretion, liver extraction ratio, and liver enhancement were measured in various in-vitro and in-vivo systems. RESULTS Mn-mesoporphyrin was soluble and stable at moderate alkaline pH in phosphate buffer. The octanol/water coefficient was 25.98, and the compound was highly protein bound. R1 for water and plasma were 1.94 and 2.35 L/mmol sec, respectively. R1 in liver was calculated to be 15.72 L/mmol sec. Biodistribution studies in rats and mice confirmed hepatotrophic properties and biliary excretion was 65% over 24 hours. First pass liver uptake was 15%. Magnetic resonance imaging studies showed persistent liver enhancement at 0.05 mmol/kg. CONCLUSION Mn-mesoporphyrin is a lipophilic compound that shows potential as a hepatobiliary magnetic resonance contrast agent.
Herbert L. Bonkovsky - One of the best experts on this subject based on the ideXlab platform.
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Hepatic 5-aminolevulinic acid synthase mRNA stability is modulated by inhibitors of heme biosynthesis and by metalloporphyrins.
European journal of biochemistry, 1996Co-Authors: Edward Earl Cable, Otto S. Gildemeister, Joyce A. Pepe, Susan E. Donohue, Richard W. Lambrecht, Herbert L. BonkovskyAbstract:Hepatic 5-aminolevulinic acid synthase, the first and normally rate-controlling enzyme of heme biosynthesis, is regulated by heme. One of the known mechanisms whereby increased cellular heme regulates 5-aminolevulinic acid synthase is by decreasing the stability of its mRNA. In primary cultures of chick embryo liver cells, we tested whether a decrease in cellular heme might increase 5-aminolevulinic acid synthase mRNA stability and whether heme or other metalloporphyrins could reverse this stabilization. We found that: (a) The stability of 5-aminolevulinic acid synthase mRNA was markedly increased by inhibitors of heme biosynthesis, namely, 4,6-dioxoheptanoic acid or deferoxamine; (b) This increased stability of 5-aminolevulinic acid synthase mRNA was reversed by the addition of heme (10 μM) or by the combination of zinc mesoporphyrin (50 nM), an inhibitor of heme oxygenase, and heme (200 nM); (c) Repression of 5-aminolevulinic acid synthase mRNA levels by zinc mesoporphyrin (10 μM) was due to inhibition of heme oxygenase, rather than a direct, heme-like, effect of zinc mesoporphyrin on 5-aminolevulinic acid synthase mRNA; (d) Among the several non-heme metalloporphyrins tested, only zinc mesoporphyrin and chromium mesoporphyrin significantly decreased 5-aminolevulinic acid synthase mRNA without increasing heme oxygenase mRNA.
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Tissue distribution of zinc-mesoporphyrin in rats: relationship to inhibition of heme oxygenase
The Journal of pharmacology and experimental therapeutics, 1995Co-Authors: Shirley M. Russo, Edward Earl Cable, Joyce A. Pepe, Susan E. Donohue, Richard W. Lambrecht, Herbert L. BonkovskyAbstract:Metalloporphyrins, including heme and others that inhibit heme oxygenase, are agents with expanding therapeutic potential. Recent results from our laboratory showed that a combination of heme and zinc-mesoporphyrin was remarkably effective in ameliorating biochemical features of acute porphyria. The aim of this study was to assess plasma clearance, tissue distribution and persistence, stability, toxicology and metabolic effects of zinc-mesoporphyrin, after its i.v. administration to rats. After administration of 15 mumol/kg b.wt. of zinc-mesoporphyrin (bound to serum albumin in a 1:1 molar ratio) the metalloporphyrin was rapidly cleared from plasma (half-life 3.6 h) with uptake primarily into liver and spleen, considerably less into the kidney and none detectable into the heart or brain. Hepatic heme oxygenase activity was undetectable for 4 days and less than 50% of control 1 week later. Inhibition of splenic heme oxygenase activity was also substantial but less marked than in the liver. No mortality was observed in any of the treated animals, and there was no detectable effect on gross or microscopic appearance of the liver, spleen, kidneys, heart, lungs or brain. Blood counts and chemistries remained within normal limits. We conclude that single doses of ZnMP-serum albumin are nontoxic, rapidly cleared from the plasma and persist primarily in the liver and spleen where heme oxygenase is inhibited for prolonged periods.