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Z L Hegedus

Publications and source records attributed to Z L Hegedus.

6 recordsLinked to original sources
PubMed1991

Para-aminophenol and structurally related compounds as intermediates in lipofuscin formation and in renal and other tissue toxicities.

P-aminophenol is considered a minor nephrotoxic metabolite of phenacetin and acetaminophen (paracetamol) in man. Our experiments show that p-aminophenol readily undergoes oxidative polymerization during incubation in human blood or plasma, to form melanin, as a component of soluble lipofuscin. Haemolysis accompanies this process in whole blood. Unmetabolized phenacetin and acetaminophen do not form soluble lipofuscins. Long-term excessive use of phenacetin or acetaminophen has been associated with chronic renal disease, haemolytic anaemia, and increased solid lipofuscin deposition in tissues. Excessive use of phenacetin has also been associated with cancer of renal pelvis and bladder. It appears to us that p-aminophenol and other o- and p-aminophenol metabolites of these drugs are intermediates not only in the etiology of chronic renal disease, but in the other developments as well. P-aminophenol and other ex(end)ogenous aminohydroxyphenyl, aminopolyhydroxyphenyl, polyhydroxyphenyl and polyaminophenyl compounds with these groups in ortho and para positions (such as 3-hydroxyanthranilic acid, 6-aminodopamine, dopamine, p-phenylenediamine, etc.) can undergo autoxidations and metal-catalyzed and enzymatic oxidations in man to produce toxic (semi)quinones(imines), (semi)quinonediimines and reactive oxygen species. After depletion of antioxidants these very reactive (semi)quinones(imines) and (semi)quinonediimine intermediates, many of which are precursors of plasma soluble lipofuscins and melanoproteins, react with essential proteins, DNA, other macromolecules and can cause or contribute to renal and other tissue toxicity, haemolytic anaemia, neoplasia, and granular lipofuscin formation. The reactive oxygen species can also deplete antioxidants, damage essential proteins, DNA, and other macromolecules, and thereby injure cells and extracellular matrix.

Adult↗
PubMed1991

Dialysis of plasma soluble lipofuscins in patients with end-stage renal failure.

Fluorescence spectrophotometry demonstrates that the levels of plasma soluble lipofuscins (SL) in patients with end-stage renal failure, undergoing continuous ambulatory peritoneal dialysis (CAPD) or haemodialysis (HD), remain significantly higher than in normal subjects. Plasma samples from these patients show the presence of SL generated from 3-hydroxy-anthranilic acid [excitation (ex) at approximately 324 nm and emission (em) at approximately 413 nm] and of other SL generated from dopa, catecholamines, 3-hydroxykynurenine and from structurally related precursors (ex at approximately 345 nm, em at approximately 445 nm). These precursors form the melanin components, which are approximately 3 wt % of SL. The fluorescence of SL appears to originate mainly from the melanin components. Peaks and shoulders at these wavelengths are found in the spectra of all dialysates. Based on intensity measurements at 413 nm and 445 nm, the weekly clearance rates with HD are in general greater than those with CAPD. The saponified cellulose ester membrane used in HD passes only lower-molecular-weight SL and/or components of SL. After HD, the greatest reductions in plasma intensities are found at approximately 324 nm and approximately 413 nm. The clearance rates (l/week) are always greater at 413 nm [means HD: 18.47 +/- 4.44 standard deviation (SD), n = 8; CAPD: 12.50 +/- 2.47, n = 4] than at 445 nm (HD: 10.94 +/- 3.86; CAPD: 7.95 +/- 1.75) both with HD and CAPD. In CAPD, the membrane also permits the passage of large amounts of albumin and other high-molecular-weight substances.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1978

Studies on rheomelanins. V. Hemolysis associated with the transformation of catechol into rheomelanin in human blood.

Incubation of 2 mg amounts of catechol in 5 ml samples of heparinated blood plasma from four subjects at 38 degrees C for 24 h produced plasma-soluble rheomelanins. These solutions had the brown color and the yellow-green fluorescence in ultraviolet light of 366 nm of other rheomelanins. Their differential ultraviolet and visible spectra showed a rheomelanin absorption maximum at 344 nm. Paper chromatograms of the rheomelanin-plasma solutions in 5% methanol-95% water showed elongated spots of rheomelanins with RF values of 0.82, on Whatman No. 1 paper. Using heparinated distilled water adjusted to pH 7.4 with sodium bicarbonate instead of human blood plasma gave markedly different findings from those obtained with the plasma rheomelanin solutions. Incubation of 4 mg amounts of catechol in 10 ml samples of heparinated whole blood from four subjects for 24, 32 and 48 at 38 degrees C produced rheomelanins as found in the plasma separated from the blood after incubation. The differential ultraviolet and visible spectra of these solutions revealed hemolysis caused by the catechol rheomelanins; this was more marked with longer incubations. The hemolysis was manifested by two absorption peaks at about 270 and 400 nm. Paper chromatography revealed the brown elongated spots of catechol rheomelanins with an RF value of 0.82. Other spots owing to the products of hemolysis were also present.

Catechols↗
PubMed1977

Studies on rheomelanins. IV. The apparent occurrence in vivo of rheomelanins in human blood.

Paper chromatograms of the rheomelanins made earlier in this laboratory in human plasmas during incubation with each of the catecholamines or with L-dopa had yellow-green fluorescence in ultraviolet light of 366 nm (Hegedus & Altschule, 1970). In the present studies, a yellow-green fluorescent spot was found in each paper chromatogram. All of these spots were eluted and their excitation and emission spectra were recorded and compared to one another. The rheomelanins made from the catecholamines, L-dopa, catechol or from mixtures of these in human plasmas during incubation were chromatographed twice on paper with two different solvent systems. These artificial rheomelanins in vitro and the apparent in vivo rheomelanins present in plasmas moved together during the two chromatographies. These yellow-green fluorescent compounds were eluted as one spot after the second chromatography. This mixture produced high intensity excitation and emission spectra closely similar to the low intensity excitation and emission spectra of the apparent in vivo rheomelanins of unincubated human plasmas treated the same way without any chemical under nitrogen. The RF-values of the various rheomelanin spots after each chromatography were closely similar. These above results were also obtained with other solvent systems. It appears therefore that rheomelanins are formed in vivo in the human body.

Dopamine↗