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PubMed2004

Porphyrins bearing mono or tripodal benzylphosphonic acid tethers for attachment to oxide surfaces.

The ability to attach redox-active molecules to oxide surfaces in controlled architectures (distance, orientation, packing density) is essential for the design of a variety of molecular-based information storage devices. We describe the synthesis of a series of redox-active molecules wherein each molecule bears a benzylphosphonic acid tether. The redox-active molecules include zinc porphyrins, a cobalt porphyrin, and a ferrocene-zinc porphyrin. An analogous tripodal tether has been prepared that is based on a tris[4-(dihydroxyphosphorylmethyl)phenyl]-derivatized methane. A zinc porphyrin is linked to the methane vertex by a 1,4-phenylene unit. The tripodal systems are designed to improve monolayer stability and ensure vertical orientation of the redox-active porphyrin on the electroactive surface. For comparison purposes, a zinc porphyrin bearing a hexylphosphonic acid tether also has been prepared. The synthetic approaches for introduction of the phosphonic acid group include derivatization of a bromoalkyl porphyrin or use of a dimethyl or diethyl phosphonate substituted precursor in a porphyrin-forming reaction. The latter approach makes use of dipyrromethane building blocks bearing mono or tripodal dialkyl phosphonate groups. The zinc porphyrin-tripodal compound bearing benzylphosphonic acid legs tethered to a SiO(2) surface (grown on doped Si) was electrically well-behaved and exhibited characteristic porphyrin oxidation/reduction waves. Collectively, a variety of porphyrinic molecules can now be prepared with tethers of different length, composition, and structure (mono or tripodal) for studies of molecular-based information storage on oxide surfaces.

Journal Article↗
PubMed1993

Urinary porphyrins as biological indicators of oxidative stress in the kidney. Interaction of mercury and cephaloridine.

Reduced porphyrins (hexahydroporphyrins, porphyrinogens) are readily oxidized in vitro by free radicals which are known to mediate oxidative stress in tissue cells. To determine if increased urinary porphyrin concentrations may reflect oxidative stress to the kidney in vivo, we measured the urinary porphyrin content of rats treated with mercury as methyl mercury hydroxide (MMH) or cephaloridine, both nephrotoxic, oxidative stress-inducing agents. Rats exposed to MMH at 5 ppm in the drinking water for 4 weeks showed a 4-fold increase in 24-hr total urinary porphyrin content and a 1.3-fold increase in urinary malondialdehyde (MDA), an established measure of oxidative stress in vivo. Treatment with cephaloridine alone (10-500 mg/kg, i.p.) produced a dose-related increase in urinary MDA and total porphyrin levels up to 1.6 and 7 times control values, respectively. Injection of MMH-treated rats with cephaloridine (500 mg/kg) caused a synergistic (20-fold) increase in urinary porphyrin levels, but an additive (1.9-fold) increase in the MDA concentration. Studies in vitro demonstrated that cephaloridine stimulated the iron-catalyzed H2O2-dependent oxidation of porphyrinogens to porphyrins in the absence of either microsomes or mitochondria. Additionally, porphyrinogens were oxidized to porphyrins in an iron-dependent microsomal lipid peroxidation system. Moreover, porphyrinogens served as an effective antioxidant (EC50 approximately 1-2 microM) to lipid peroxidation. These results demonstrate that MMH and cephaloridine synergistically, as well as individually, promote increased oxidation of reduced porphyrins in the kidney and that this action may be mechanistically linked to oxidative stress elicited by these chemicals. Increased urinary porphyrin levels may, therefore, represent a sensitive indicator of oxidative stress in the kidney in vivo.

Animals↗
PubMed1993

Kinetics of porphyrin accumulation in cultured epithelial cells exposed to ALA.

1. The kinetics of porphyrin accumulation in cultured mammalian epithelial cells (CNCM-I-221) during exposure to ALA was investigated. 2. The total porphyrin synthesized is a function of ALA concentration and the incubation time. The cellular porphyrin content exhibited a saturation pattern, reaching a plateau at about 0.04 fmol porphyrins/cell. A biphasic time-dependent increase in the total porphyrin synthesized was observed. 3. After 3 hr of exposure to ALA the rate of synthesis increased to almost twice the initial rate, reaching between 0.02 and 0.05 fmol porphyrins/cell/hr depending on serum concentration in the medium. 4. Two effects of FBS on ALA-stimulated porphyrin accumulation were observed. Greater total porphyrin synthesis was found when incubations were made in 10% FBS compared to those in 1% FBS. 5. The higher serum concentration also caused a greater release into the medium of the porphyrins generated in the cells with a calculated half-life of 24 min in 10% serum-supplemented medium compared with 62 min in 1% serum. 6. The results obtained from cell synchronization experiments suggest that there is little obvious cell cycle-dependent variation in the synthesis of porphyrins from ALA. 7. The small differences in the intracellular porphyrin content that were observed may be attributed to a slight reduction in the rate of loss of porphyrins in G2/M cells.

Aminolevulinic Acid↗
PubMed1995

Efficiency of three different hemodialysis membranes for plasma porphyrin removal.

To assess the capability of three different membranes to remove porphyrins, plasma and dialysate porphyrin levels were fluorometrically measured in 10 patients with end-stage renal failure who were on hemodialysis. Three different hemodialysis membranes were used: cuprophan, polyacrylonitrile, and cellulose triacetate. Total plasma porphyrin concentrations decreased after dialysis, but to a lesser extent when using the cuprophan membrane (19%) than with the polyacrylonitrile (26%) or cellulose triacetate (30%) membranes (P < 0.01). However, since the free plasma porphyrin fraction remained unchanged, it can be assumed that the equilibrium between protein-bound and non-protein-bound (free) porphyrins is displaced toward the latter fraction. Dialysate porphyrin levels were lower (P < 0.01) when using the cuprophan membrane (10.1 micrograms/session) than when using polyacrylonitrile (17.8 micrograms/session) and cellulose triacetate (21.9 micrograms/session). Although most of the plasma porphyrins are protein bound, our results show that hemodialysis can remove significant amounts of non-protein-bound (free) porphyrins. The polyacrylonitrile and cellulose triacetate membranes had a greater capacity for porphyrin removal than cuprophan. Thus, two high-permeability membranes (polyacrylonitrile and cellulose triacetate) should be used whenever a reduction of plasma porphyrin levels is desired.

Acrylic Resins↗
PubMed1993

Salivary porphyrin concentration in porphyria cutanea tarda.

To assess the clinical utility of saliva samples, serum, urine and saliva porphyrin concentration were fluorometrically measured in 31 patients with porphyria cutanea tarda. In comparison with normal values, porphyrin mean levels were 20-fold increased in serum and urine but only 3-fold in saliva. Saliva porphyrin concentration exhibited significant but weak correlations with porphyrin levels in serum (r = 0.69) and urine (r = 0.67). However, saliva porphyrins were not more closely correlated with protein-unbound serum porphyrins (r = 0.57). This finding suggests that saliva porphyrin concentration does not simply correspond to the filtered free fraction of serum porphyrins. Nevertheless, measurement of saliva porphyrins could represent a valuable non-invasive alternative to serum porphyrins in the monitoring of patients with porphyria cutanea tarda.

Fluorometry↗
PubMed2005

Photoinactivation of Escherichia coli using porphyrin derivatives with different number of cationic charges.

The photodynamic effect of meso-substituted cationic porphyrins, 5-[4-(trimethylammonium)phenyl]-10,15,20-tris(2,4,6-trimethoxyphenyl)porphyrin iodide 1, 5,10-di(4-methylphenyl)-15,20-di(4-trimethylammoniumphenyl)porphyrin iodide 2 and 5-(4-trifluorophenyl)-10,15,20-tris(4-trimethylammoniumphenyl)porphyrin iodide 3, have been investigated in both homogeneous medium bearing photooxidizable substrates and in vitro on a typical gram-negative bacterium Escherichia coli. Absorption and fluorescence spectroscopic studies were compared in N,N-dimethylformamide. Fluorescence quantum yields (varphiF) of 0.10, 0.06 and 0.08 were calculated for porphyrins 1, 2 and 3, respectively. The singlet molecular oxygen, O2(1Deltag), production was evaluated using 9,10-dimethylanthracene yielding values of 0.66, 0.36 and 0.42 for porphyrins 1, 2 and 3, respectively. Guanosine 5'-monophosphate was used as biological substrate model. Similar decomposition of guanosine 5'-monophosphate was obtained using these cationic porphyrins as sensitizer. In biological medium, photosensitized inactivation of E. coli was analyzed using cells without and with one washing step. E. coli cultures were treated with sensitizer at 37 degrees C for 30 min in dark. In both procedures, a higher photoinactivation of cells (>99.999%) was found for cells treated with 10 microM of tricationic porphyrin 3 and irradiated for 5 min with visible light. Porphyrins 1 and 2 only show an important photodamage when the cells are irradiated without washing step. These results indicated that the tetracationic porphyrin 3 could be a promising sensitizer with potential applications in the photoinactivation of bacterial cells by photodynamic therapy.

Anthracenes↗
PubMed2001

The 5-aminolevulinic acid-induced porphyrin biosynthesis in benign and malignant cells of the skin.

In fluorescence diagnosis and photodynamic therapy of neoplastic tissues 5-aminolevulinic acid is used to synthesize endogenous porphyrins as photosensitizers. The efficacy of neoplastic tissues to fluorescence diagnosis and photodynamic therapy is thought to be dependent on the total level of intralesional formed porphyrins. The available profiles of porphyrin metabolites in normal and in neoplastic cell lines after administration of 5-aminolevulinic acid vary considerably. Thus, this is the first in-vitro study which compares the porphyrin biosynthesis in normal skin cells (HaCaT, fibroblasts) with melanoma cells (Bro, SKMel-23, SKMel-28). After incubation with 1 mM 5-aminolevulinic acid, kinetics of porphyrin levels and metabolites were determined in the cells and the corresponding supernatants. Exogenous 5-aminolevulinic acid induced porphyrin formation in all cells with maximum values after an incubation period of 16-36 h. Increase of porphyrin levels varied from 10- to 80-fold (SKMel-28>HaCaT>fibroblasts>SKMel-23>>Bro) with minimum 1.5 times higher levels of porphyrins in the supernatants than in the cells. In cells and supernatants protoporphyrin and coproporphyrin were the predominantly formed porphyrin metabolites. Metastatic melanoma cells (SKMel-23, SKMel-28) accumulated much higher porphyrin levels than primary melanoma cells (Bro). In conclusion, by optimizing the treatment modalities, especially the light source, topical photodynamic therapy (PDT) could become a treatment alternative of melanoma metastases in progressive disease.

Aminolevulinic Acid↗
PubMed2004

Structural, NMR, and EPR studies of S = (1)/(2) and S = (3)/(2) Fe(III) bis(4-cyanopyridine) complexes of dodecasubstituted porphyrins.

The NMR and EPR spectra for three complexes, iron(III) octamethyltetraphenylporphyrin bis(4-cyanopyridine) perchlorate, [FeOMTPP(4-CNPy)(2)]ClO(4), and its octaethyl- and tetra-beta,beta'-tetramethylenetetraphenylporphyrin analogues, [FeOETPP(4-CNPy)(2)]ClO(4) and [FeTC(6)TPP(4-CNPy)(2)]ClO(4), are presented. The crystal structures of two different forms of [FeOETPP(4-CNPy)(2)]ClO(4) and one form of [FeOMTPP(4-CNPy)(2)]ClO(4) are also reported. Attempts to crystallize [FeTC(6)TPP(4-CNPy)(2)]ClO(4) were not successful. The crystal structure of [FeOMTPP(4-CNPy)(2)]ClO(4) reveals a saddled porphyrin core, a small dihedral angle between the axial ligand planes, 64.3 degrees, and an unusually large tilt angle (24.4 degrees ) of one of the axial 4-cyanopyridine ligands with respect to the normal to the porphyrin mean plane. There are 4 and 2 independent molecules in the asymmetric units of [FeOETPP(4-CNPy)(2)]ClO(4) crystallized from CD(2)Cl(2)/dodecane (1-4) and CDCl(3)/cyclohexane (5-6), respectively. The geometries of the porphyrin cores in 1-6 vary from purely saddled to saddled with 15% ruffling admixture. In all structures, the Fe-N(p) distances (1.958-1.976 A) are very short due to strong nonplanar distortion of the porphyrin cores, while the Fe-N(ax) distances are relatively long ( approximately 2.2 A) compared to the same distances in S = (1)/(2) bis(pyridine)iron(III) porphyrin complexes. An axial EPR signal is observed (g( perpendicular ) = 2.49, g( parallel ) = 1.6) in frozen solutions of both [FeOMTPP(4-CNPy)(2)]ClO(4) and [FeTC(6)TPP(4-CNPy)(2)]ClO(4) at 4.2 K, indicative of the low spin (LS, S = (1)/(2)), (d(yz)d(xz))(4)(d(xy))(1) electronic ground state for these two complexes. In agreement with a recent publication (Ikeue, T.; Ohgo, Y.; Ongayi, O.; Vicente, M. G. H.; Nakamura, M. Inorg. Chem. 2003, 42, 5560-5571), the EPR spectra of [FeOETPP(4-CNPy)(2)]ClO(4) are typical of the S = (3)/(2) state, with g values of 5.21, 4.25, and 2.07. A small amount of LS species with g = 3.03 is also present. However, distinct from previous conclusions, large negative phenyl-H shift differences delta(m) - delta(o) and delta(m) - delta(p) in the (1)H NMR spectra indicate significant negative spin density at the meso-carbons, and the larger than expected positive average CH(2) shifts are also consistent with a significant population of the S = 2 Fe(II), S = (1)/(2) porphyrin pi-cation radical state, with antiferromagnetic coupling between the metal and porphyrin unpaired electrons. This is the first example of this type of porphyrin-to-metal electron transfer to produce a partial or complete porphyrinate radical state, with antiferromagnetic coupling between metal and macrocycle unpaired electrons in an iron porphyrinate. The kinetics of ring inversion were studied for the [FeOETPP(4-CNPy)(2)]ClO(4) complex using NOESY/EXSY techniques and for the [FeTC(6)TPP(4-CNPy)(2)]ClO(4) complex using DNMR techniques. For the former, the free energy of activation, deltaG, and rate of ring inversion in CD(2)Cl(2) extrapolated to 298 K are 63(2) kJ mol(-)(1) and 59 s(-)(1), respectively, while for the latter the rate of ring inversion at 298 K is at least 4.4 x 10(7) s(-)(1), which attests to the much greater flexibility of the TC(6)TPP ring. The NMR and EPR data are consistent with solution magnetic susceptibility measurements that show S = (3)/(2) in the temperature range from 320 to 180 K for [FeOETPP(4-CNPy)(2)](+), while both [FeOMTPP(4-CNPy)(2)](+) and [FeTC(6)TPP(4-CNPy)(2)](+) change their spin state from S = (3)/(2) at room temperature to mainly LS (S = (1)/(2)) upon cooling to 180 K.

Chloroform↗
PubMed2004

Structure and photophysical properties of porphyrin-modified metal nanoclusters with different chain lengths.

Three-dimensional porphyrin-monolayer-protected gold clusters with different chain lengths (MPCs) have been prepared to examine the structure and photophysical properties, in comparison with self-assembled monolayers (SAMs) of the porphyrins on a flat gold surface. The three-dimensional porphyrin MPCs exhibit electrochemical and photophysical properties that are much closer to those of a porphyrin reference compound in solution than those of two-dimensional porphyrin SAMs on the flat gold surface. The three-dimensional architectures of porphyrin MPCs with large surface area have improved the light-harvesting efficiency relative to the corresponding porphyrin SAM on the two-dimensional flat gold surface. Time-resolved single photon counting fluorescence and transient absorption spectroscopic studies have demonstrated that undesirable quenching of the porphyrin excited singlet state via energy transfer to the gold surface of the three-dimensional MPCs is much suppressed, as compared to the quenching of the porphyrin SAMs on the two-dimensional flat gold surface. Both the quenching rate constants of the porphyrin excited singlet state by the surfaces of bulk gold and gold nanoclusters reveal weak chain length dependence of the energy transfer quenching.

Gold↗
PubMed1991

Bile porphyrin analysis in the evaluation of variegate porphyria.

BACKGROUND: Variegate porphyria is a genetic disorder of porphyrin metabolism in which patients may have both neurologic dysfunction and photocutaneous lesions. Biochemical confirmation of the diagnosis can be difficult, particularly in patients without neurologic dysfunction at the time of testing. The demonstration of increased fecal excretion of porphyrin is frequently used for this purpose, but levels may be normal. Since elevated fecal porphyrin levels in variegate porphyria are presumably a consequence of increased biliary excretion, we evaluated whether analysis of porphyrins in bile distinguishes better between patients with variegate porphyria and controls. METHODS: Bile samples were collected by duodenal aspiration from 10 patients with proved variegate porphyria who had no neurologic symptoms when they were studied and 17 control subjects. Bile and fecal porphyrin levels were measured fluorometrically. RESULTS: The mean total porphyrin concentration in bile in the patients with variegate porphyria was significantly higher than that in the controls (67.8 vs. 0.71 mumol per liter; P less than 0.00002). There was more than a ninefold difference between the highest level in any control subject and the lowest level in any patient with variegate porphyria. The mean fecal porphyrin level in the patients with variegate porphyria also differed significantly from that in the controls (0.79 vs. 0.14 mumol per gram of dry weight; P less than 0.007), but four patients had levels within the control range. CONCLUSIONS: The concentration of porphyrin in bile is higher in patients with variegate porphyria than in controls, and the difference is greater than that for fecal porphyrin. Bile porphyrin measurements may be helpful in the evaluation of asymptomatic patients suspected of having variegate porphyria.

Adolescent↗
PubMed2001

Quantitative evaluation of urinary porphyrins as a measure of kidney mercury content and mercury body burden during prolonged methylmercury exposure in rats.

Changes in urinary porphyrin excretion patterns (porphyrin profiles) during prolonged mercury exposure are attributable to mercury accumulation in the kidney and to consequent effects of Hg2+ on renal porphyrin metabolism. In the present study, we evaluated the quantitative relationship of urinary porphyrin concentrations to mobilizable renal mercury content, using the metal chelator 2,3-dimercapto-1-propanesulfonic acid (DMPS) to modulate kidney mercury levels. Rats exposed to methylmercury hydroxide (MMH) at 10 ppm in drinking water for 6 weeks were treated with up to 3 consecutive doses of DMPS (100mg/kg, ip) at 72-h intervals. Consistent with previous findings, the concentrations of pentacarboxyl- (5-) and copro- (4-) porphyrins and of an atypical porphyrin specific to mercury exposure, precoproporphyrin, were significantly elevated in urine of MMH-exposed rats, compared with that of rats exposed to distilled water (dH2O) for the same period. Consecutive DMPS treatments of MMH-exposed rats significantly decreased kidney concentrations of total, as well as Hg2+ and CH3Hg+ species, and promoted increased urinary mercury excretion. Concomitantly, DMPS treatment decreased both kidney and urinary porphyrin concentrations, consistent with depletion of renal mercury levels. Regression analyses demonstrated a high correlation (r approximately 0.9) between prechelation urinary porphyrins and postchelation urinary mercury levels and also between prechelation urinary porphyrins and prechelation kidney mercury concentrations. These findings demonstrate that urinary porphyrin concentrations relate quantitatively to DMPS-mobilizable mercury in the kidney and, therefore, serve as a biochemical measure of renal mercury content.

Animals↗
PubMed1982

Investigation of the membrane-fluidizing properties of porphyrin-inducing drugs.

The objective of this study was to test the hypothesis that porphyrin-inducing drugs act at least in part by disrupting membrane lipids. The porphyrin-inducing steroids, 3 alpha-hydroxy-5 alpha-pregnane-11,20-dione (alfaxalone) and 3 alpha-hydroxy-5 alpha-pregnan-20-one induce considerably greater fluidity changes in spin-labelled phospholipid-cholesterol bilayers than do the corresponding 3 beta-hydroxy steroids which are also less potent as porphyrin inducers. The steroids did not cause any significant change in spin-labelled vesicles lacking cholesterol. The porphyrin-inducing compound 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine and a series of analogues caused fluidity changes in phospholipid bilayers in the presence and absence of cholesterol. The porphyrin-inducing nonplanar 2,2',4,4'-6,6'-hexachlorobiphenyl caused a significant change in bilayer fluidity in phospholipid bilayers in the presence and absence of cholesterol. Since the planar 3,3',4,4'-tetrachlorobiphenyl, allylisopropylacetamide (AIA), and griseofulvin are potent porphyrin-inducing compounds, but do not fluidize a lipid bilayer, it was clear that the original hypothesis required modification. No evidence could be obtained to support the idea that a subset of porphyrin-inducing drugs exists which are membrane fluidizers and whose common mechanism of action as porphyrin-inducers might be revealed by a common pattern of porphyrin accumulation in chick embryo liver cells. It is suggested that those porphyrin-inducing compounds with membrane-fluidizing properties might fluidize the nuclear membrane, thus facilitating the transfer of an induction specific RNA for delta-aminolevulinic acid synthetase from the nucleus to the cytoplasm.

Allylisopropylacetamide↗
PubMed1996

Accumulation of porphyrins in plasma and tissues of dogs after delta-aminolevulinic acid administration: implications for photodynamic therapy.

Protoporphyrin accumulates in tissues after administration of delta-aminolevulinic acid, and can be used as a photosensitizer for photodynamic therapy. To determine the distribution of porphyrins in a large animal model after administration of this porphyrin precursor, delta-aminolevulinic acid was administered to anesthetized dogs (100 mg/kg body weight intravenously) and porphyrin concentrations were measured in tissues (liver, pancreas, prostate, bladder, muscle and skin), plasma and urine for 6-10 h. Porphyrins increased markedly (up to 50-fold) in plasma within 1 h, were still markedly increased at 8 h, and consisted mostly of coproporphyrin III and protoporphyrin. Tissue porphyrin concentrations increased more slowly, were highest in liver, pancreas and prostate 7-10 h after delta-aminolevulinic acid administration, and were predominantly protoporphyrin. Maximum porphyrin concentrations in liver were 3- and 4-fold higher than in pancreas and prostate, respectively. Urinary delta-aminolevulinic acid excretion increased and was greatest 2-4 h after dosing; urinary porphobilinogen and porphyrins increased more gradually and remained increased up to at least 8 h. Coproporphyrin III was the predominant porphyrin in urine at all times, but hepta-, hexa- and pentacarboxyl porphyrins increased proportionally after administration of delta-aminolevulinic acid. These results indicate that porphyrins accumulate in plasma as well as tissues and urine after administration of delta-aminolevulinic acid, and may contribute to tumor necrosis during photodynamic therapy.

Aminolevulinic Acid↗
PubMed1997

Effects of new anticonvulsant medications on porphyrin synthesis in cultured liver cells: potential implications for patients with acute porphyria.

Some patients with acute hereditary porphyrias have seizures and require anticonvulsant therapy, but many anticonvulsants induce exacerbations of the hepatic porphyrias. Recently, several new anticonvulsants have become available. Among these are gabapentin, vigabatrin, felbamate, lamotrigine, and tiagabine. Little is known about their potential for induction of porphyric attacks. We used a cell culture model of primary chicken embryo liver cells, which maintain intact heme synthesis and regulation, to study the effects of these new anticonvulsants on porphyrin accumulation. Treatment of the cells with deferoxamine (250 microM) led to a partial block in heme synthesis, simulating the conditions encountered in human beings with porphyria. Concomitant exposure of these cells to phenobarbital (2 mM) strongly induced accumulation of porphyrins, serving as a positive control in this model. Cells were treated for 20 hours with increasing doses (3.2 to 1,000 microM) of the newer anticonvulsants, with or without deferoxamine. For most of these anticonvulsants 5 to 100 microM is representative of the concentrations achieved in humans with therapeutic doses. Porphyrins were measured spectrofluorometrically as uro-, copro-, and protoporphyrins. Results were confirmed by high-pressure liquid chromatography. Neither vigabatrin nor gabapentin treatment, with or without deferoxamine, led to any increase in porphyrin accumulation. Similar doses of felbamate (with deferoxamine) led to a marked increase in (mainly proto-) porphyrin levels, qualitatively and quantitatively almost identical to the accumulation produced by phenobarbital. Lamotrigine or tiagabine (with deferoxamine) caused similar porphyrin accumulation. Tiagabine treatment up to 100 microM (with deferoxamine) also resulted in very high levels of predominantly proto-porphyrin. In contrast to the other anticonvulsants tested, tiagabine without deferoxamine led to mild porphyrin accumulation. In the presence of deferoxamine, phenobarbital, felbamate, lamotrigine, or tiagabine, but not gabapentin or vigabatrin, increased levels of the mRNA of ALA synthase, the first and rate-controlling enzyme of porphyrin synthesis. Such enzyme induction is a sine qua non for acute porphyric attacks. We conclude that neither vigabatrin nor gabapentin is porphyrogenic, whereas felbamate, lamotrigine, and, especially, tiagabine lead to much accumulation of porphyrins. The latter three anticonvulsants, therefore, may precipitate or exacerbate acute porphyric attacks in humans. We recommend use of vigabatrin or gabapentin, but not felbamate, lamotrigine, or tiagabine, in patients with acute porphyria and seizures.

Animals↗
PubMed2002

Evaluation of urinary porphyrin excretion in neonates born to mothers exposed to airborne hexachlorobenzene.

The existence of a link between hexachlorobenzene (HCB) and porphyria cutanea tarda has been known for a long time. However, the epidemiologic data on effects on health caused by prenatal exposure have not provided convincing evidence that HCB alters porphyrin metabolism. Our objectives were to analyze urinary porphyrin excretion and HCB in maternal serum and fetal cord blood in neonates born in a village (Flix) near a chlorinated solvent factory, to detect possible adverse effects in urinary porphyrin excretion caused by prenatal exposure, and to assess their relationship with HCB blood levels. We conducted a cross-sectional study in the Porphyria Unit at a tertiary care facility in Barcelona, Spain, and the Pediatric Unit of the Móra d'Ebre Hospital, the reference hospital of the study area. We included in the study all neonates (n = 68) born in Móra d'Ebre Hospital 1997-1999 and their mothers. We obtained 68 urine specimens of singleton neonates on the third day after birth to test for urinary porphyrin excretion. We obtained 52 fetal cord blood and 56 maternal serum samples for HCB analysis. Total urinary porphyrins were quantified using spectrofluorometry. Porphyrin profile was determined by HPLC. Serum HCB was analyzed by gas chromatography coupled with electron capture detection. In total population, median HCB levels were 1.08 ng/mL in cord blood and 3.31 ng/mL in maternal serum. Total urinary porphyrin concentration was 37.87 micromol/mol creatinine. Coproporphyrin I and coproporphyrin III were the major porphyrins excreted. We found no positive relationship between urinary porphyrin excretion and HCB levels. However, we observed an association between maternal smoking and coproporphyrin excretion. Although high environmental levels of HCB are reported in the town of Flix, we found no alteration in urinary porphyrin excretion.

Adult↗
PubMedDate not supplied

In situ assessment of porphyrin photosensitizers in Propionibacterium acnes.

Porphyrins are known to be efficient photosensitizer molecules and the combined action of light and porphyrins in Propionibacterium acnes have a lethal action on the cells. Identification and quantification of in situ porphyrins in P. acnes have been done using an integrating sphere connected to an ordinary absorption spectrophotometer, and the amounts of porphyrins in the cells were quantified by measuring scattering free absorption spectra of the cell suspensions. The concentration of porphyrins in P. acnes cells were increased in either of two ways; by the addition of delta-aminolevulinic acid (ALA), which lead to the formation of coproporphyrin III under the incubation conditions used in these experiments, or by the addition of protoporphyrin IX (PPIX) to the cell suspension. In the latter case, PPIX molecules are taken up by the cells in a membrane-mediated uptake mechanism, and accumulate in the cells either on a monomeric or a particular aggregate form. The fraction of porphyrins on aggregate form increased with increasing PPIX additions. In the case of ALA induced porphyrin production, only monomeric porphyrins were stored in the cells. In both cases, the cells have a limited binding capacity of monomeric porphyrins, which is estimated to be 3 x 10(5) molecules/cell, or one porphyrin molecule to every 100st lipid molecule in the cell membrane.

Aminolevulinic Acid↗
PubMed1992

Removal of plasma porphyrins with high-flux hemodialysis in porphyria cutanea tarda associated with end-stage renal disease.

Plasma porphyrin levels are markedly increased in patients with porphyria cutanea tarda (PCT) associated with end-stage renal disease. Conventional hemodialysis (CHD) with lower blood flow rates (less than 250 mL/min) and cuprophan or cellulose acetate membranes is ineffective in removing significant amounts of porphyrins in this condition. Changes in plasma porphyrin levels and porphyrin clearances during hemodialysis with higher blood flow rates and more-permeable, high-efficiency cellulose acetate and high-flux polysulfone dialyzers were evaluated in a chronic hemodialysis patient with PCT and markedly elevated plasma porphyrins. The polysulfone membrane achieved significantly better fractional porphyrin removal (P = 0.02) and porphyrin clearances (P less than 0.01) than did the high-efficiency cellulose acetate membrane. After conversion from maintenance CHD with a standard cellulose acetate dialyzer to a 4-wk period of high-flux hemodialysis (HFHD) with a polysulfone dialyzer, predialysis plasma porphyrins fell by 37%. After returning to CHD, plasma porphyrins returned to the higher prestudy levels. These observations suggest that HFHD with more permeable membranes and higher blood flow rates removes porphyrins more effectively than does CHD. HFHD may be a useful adjunct to other measures used in treating dialysis patients with PCT.

Cellulose↗
PubMed1994

Effect of porphyrin and irradiation on heme biosynthetic pathway in endothelial cells.

To study porphyrin biosynthesis in human umbilical vein endothelial cells (EC), cultured EC were incubated with delta-aminolevulinic acid (ALA), the precursor of porphyrin synthesis, and porphyrins generated were measured spectrofluorometrically. EC accumulated porphyrins in an incubation time-dependent and ALA dose-dependent fashion. Porphyrin accumulation was enhanced by CaMg EDTA, a ferrochelatase inhibitor, suggesting the participation of ferrochelatase. The effect of porphyrin and irradiation on porphyrin accumulation was evaluated by exposing porphyrin-containing EC to the UVA and blue light, followed by incubation with ALA for 2-48 h. Decreased porphyrin accumulation 2-48 h after the irradiation was noted at all the time-points examined. However, no alteration of ferrochelatase activity was observed, suggesting that the decrease in porphyrin levels was due to suppression of the activity of the other enzymes in the earlier steps of the heme biosynthetic pathway.

Aminolevulinic Acid↗