Biomedical subjects

M Chevion

Publications and source records attributed to M Chevion.

At least 37 records · Page 2Linked to original sources

PubMed1997

Protective effects of tea polyphenols against oxidative damage to red blood cells.

Tea polyphenols (TPP) from black and green teas were evaluated for their antioxidant effects on normal red blood cells (RBC) and beta-thalassemic RBC membranes challenged with exogenous oxidants in vitro. The TPP of both types protected RBC against primaquine-induced lysis; they also protected the whole cells and the membranes against H2O2-induced lipid peroxidation so that about 80% protection was reached at [TPP] = 10 microg/mL. TPP from black tea at the same concentration protected normal RBC from morphological alterations caused by the peroxide treatment. The mechanism of the effects of TPP was investigated using a chemical system generating .OH (iron + ascorbic acid). TPP from both black and green teas inhibited the .OH fluxes in a concentration-dependent manner, indicating the possibility of iron chelation by TPP. Spectrophotometric titration revealed that TPP could stoichiometrically bind ferric iron to form a redox-inactive Fe-TPP complex. Quantitative analysis suggests that one or more major catechins from the TPP preparations are the likely iron-binding compounds accounting for the antioxidant effects of TPP on RBC.

Antioxidants↗

PubMed1997

Antioxidant activity of rat parotid saliva.

BACKGROUND: The healing-promotion property of saliva has been observed in the past, but its underlying mechanism has never been elucidated. We hypothesized a mechanism based on salivary proteins binding to redox active metal ions, rendering them nonactive in their capacity for free radical production. METHODS: Examination of this mechanism was conducted by comparing the redox activity of protein-rich saliva with protein-poor saliva. We also examined the redox activity mediated by these 2 kinds of saliva following the in vitro addition of iron, copper, and manganese. Saliva samples were analyzed for their redox activity by measuring the ascorbate-driven and saliva (diluted 1:2)-mediated conversion of salicylate to its 2,3- and 2.5-dihydroxybenzoates and catechol metabolites. RESULTS: The concentrations of salicylate metabolites formed by protein-rich saliva were significantly lower by 45% (P < .05), 66% (P < .01), and 54% (P < .05), respectively, when compared with those formed by protein-poor saliva. The capacity of saliva in suppressing redox activity was found to be inversely related to the concentrations of iron and copper added (but not manganese), but correlated well with the protein content. When the highest concentrations of iron (15 mumol/L) and copper (10 mumol/L) were added to protein-rich saliva, the concentrations of salicylate metabolites produced were only 0.3% to 1% of those of non-saliva-containing controls (P < .01). However, when these concentrations of iron and copper were added to protein-poor saliva, significantly higher values of redox activity were detected, and the concentrations of the salicylate derivatives produced were 2.1% to 8.1% of those of non-saliva-containing controls (P < .01). In contrast, when the lowest concentrations of iron (2 mumol/L) and copper (0.1 mumol/L) were added, 2.8 to 4 times lower concentrations of salicylate derivatives were produced (P < .01). CONCLUSION: These results substantiate our hypothesis that saliva has a profound capacity for reducing redox activity rendered by transition metal ions, correlating well with its protein content.

Ancitabine↗

PubMed1997

Patterns of mobilization of copper and iron following myocardial ischemia: possible predictive criteria for tissue injury.

Direct evidence for substantial iron and copper mobilization into the coronary flow immediately following prolonged, but not short, cardiac ischemia is presented. When small volumes of coronary flow fractions (CFFs) were serially collected upon reperfusion, after 25-60 min of ischemia, the copper and iron levels in the first CFF were 50-fold and 12- to 15-fold higher, respectively, than corresponding pre-ischemic values. The copper and iron levels after shorter periods (15-21 min) of ischemia were only about five-fold higher than the pre-ischemic values. This demonstrates that the resumption of coronary flow is accompanied by a burst of both metal ions. The levels of Cu/Fe in the CFFs correlated well with the loss of cardiac function following global ischemia of varying duration. After 18 min of ischemia, the residual cardiac function was less than 50%, and the damage was essentially reversible. After 25 min of ischemia, it exceeded 50% and was only partially reversible, while after 35 min, the damage exceeded 80%, and was mostly irreversible. The results are in accord with the hypothesis that copper and iron play causative roles in myocardial injury through mediation of hydroxyl radical production. Thus, the pattern of Cu/Fe mobilization from the tissue into the CFF can be used for the prediction of the severity of myocardial damage following ischemia, and could be developed into useful modalities for intervention in tissue injury.

Animals↗

PubMed1997

The antioxidant properties of thioctic acid: characterization by cyclic voltammetry.

Thioctic acid (TA) level and its antioxidant capacity were monitored by cyclic voltammetry (CV), in solution and in human plasma. A linear correlation between the anodic wave current Ia at 900 mV and [TA] was obtained. This indicates that TA, commonly found in human plasma, is an antioxidant component characterized by a potential E1/2 = 900 mV and constitute, at least in part, the second anodic wave of the CV tracing. When plasma from diabetic patients was analyzed by CV, those patients under treatment with TA showed higher Ia than others not taking the drug. When the patients under treatment with TA were divided into groups according to the severity of their nephropathy, or according to the severity of their total complication count, Ia levels representing TA were significantly higher in those patients with more severe complications.

Adult↗

PubMed1997

Halothane prevents postischemic production of hydroxyl radicals in the canine heart.

BACKGROUND: Recent studies indicate that during regional myocardial ischemia and subsequent reperfusion, volatile anesthetics may provide protection against free radical-related injury. The effect of halothane on free radical production during ischemia and reperfusion, in the canine heart, was investigated. The level of hydroxyl radical (.OH)-mediated conversion of salicylate to its dehydroxybenzoate derivatives (2,3-DHBA and 2,5-DHBA) was monitored. METHODS: Under general anesthesia, the heart was exposed through median sternotomy. Salicylate (100 mg/kg given intravenously) was administered 30 min before left anterior descending artery occlusion. Six dogs were studied using inhaled halothane (1.6%) 10 min before and during the 10-min ischemic period, followed by 50 min of reperfusion, and then they were compared with seven other dogs used as controls. Blood concentrations of salicylate, 2,3-DHBA and 2,5-DHBA, K+, lactate, oxygen content, and pH were monitored. RESULTS: An acute increase in the normalized concentrations of 2,3-DHBA and 2,5-DHBA was observed in the control animals during reperfusion. In contrast, halothane inhalation completely inhibited the production of both metabolites (P < 0.02), but 2,5-DHBA concentrations in the halothane-treated group were even less than the basal level (P < 0.05). The increase in lactate concentrations in the experimental animals was significantly less than that of controls (P < 0.05) and followed the same time-dependent pattern as the changes in K+ and pH. Halothane significantly decreased (P < 0.0001) the difference in oxygen content between coronary sinus and aortic root blood, suggesting decreased oxygen utilization during reperfusion. CONCLUSIONS: Halothane completely inhibited the production of .OH, and its administration may protect the heart from the deleterious effect of oxygen-derived reactive species, with attenuation of the metabolic response to ischemia.

Anesthetics, Inhalation↗

PubMed1997

Advanced glycation end product-induced activation of NF-kappaB is suppressed by alpha-lipoic acid in cultured endothelial cells.

Depletion of cellular antioxidant defense mechanisms and the generation of oxygen free radicals by advanced glycation end products (AGEs) have been proposed to play a major role in the pathogenesis of diabetic vascular complications. Here we demonstrate that incubation of cultured bovine aortic endothelial cells (BAECs) with AGE albumin (500 nmol/l) resulted in the impairment of reduced glutathione (GSH) and ascorbic acid levels. As a consequence, increased cellular oxidative stress led to the activation of the transcription factor NF-kappaB and thus promoted the upregulation of various NF-kappaB-controlled genes, including endothelial tissue factor. Supplementation of the cellular antioxidative defense with the natural occurring antioxidant alpha-lipoic acid before AGE albumin induction completely prevented the AGE albumin-dependent depletion of reduced glutathione and ascorbic acid. Electrophoretic mobility shift assays (EMSAs) revealed that AGE albumin-mediated NF-kappaB activation was also reduced in a time- and dose-dependent manner as long as alpha-lipoic acid was added at least 30 min before AGE albumin stimulation. Inhibition was not due to physical interactions with protein DNA binding, since alpha-lipoic acid, directly included into the binding reaction, did not prevent binding activity of recombinant NF-kappaB. Western blots further demonstrated that alpha-lipoic acid inhibited the release and translocation of NF-kappaB from the cytoplasm into the nucleus. As a consequence, alpha-lipoic acid reduced AGE albumin-induced NF-kappaB mediated transcription and expression of endothelial genes relevant in diabetes, such as tissue factor and endothelin-1. Thus, supplementation of cellular antioxidative defense mechanisms by extracellularly administered alpha-lipoic acid reduces AGE albumin-induced endothelial dysfunction in vitro.

Antioxidants↗

PubMed1997

Nitroxide radicals prevent metal-aggravated reperfusion injury in isolated rat heart.

The effects of Cu(II) and the stable nitroxide radical 4-OH-2, 2, 6, 6-tetramethyl-piperidine-1-oxyl (TPL) on reperfusion injury following global myocardial ischemia have been studied using the isolated rat heart model in the Langendorff configuration. Hearts were equilibrated with Krebs-Henseleit buffer (KH-buffer) for 10 min and subjected to 18 min of normothermic global ischemia. After 20 min reperfusion, hemodynamic parameters recovered as follows: ventricular developed pressure (77%), dP/dt (71%) and -dP/dt (80%), heart rate (91%), and work index (70%). End-diastolic pressure was 16 mm Hg. When 10 microM Cu-nitrilotriacetate or Cu-(histidine)2 was included in the perfusate before, during, and following ischemia, the heart injury was more extensive and the work index only recovered to 17% of the preischemic value. The inclusion of 100 microM TPL during reperfusion abolished the copper-induced sensitization. In the absence of copper, TPL did not provide any protection against ischemia-reperfusion damage to the heart. The inclusion of 100 microM 1,4-dihydroxy-2,2,6,6-tetramethylpiperidine (TPL-H) during reperfusion, partially abolished the copper-induced sensitization. Since conversion between TPL and TPL-H takes place, the fact that both forms provide protection can increase their protective efficacy.

Animals↗

PubMed1997

Irradiation-induced damage to the salivary glands: the role of redox-active iron and copper.

The mechanism of irradiation-induced hypofunction of the salivary glands is a process that is not fully understood. Here we examine the hypothesis that intracellular and redox-active ions of iron and copper, which are associated with the secretion granules, play a catalytic role in the irradiation-induced damage. Rats were subjected to head and neck irradiation (15 Gy X rays) and allowed to recover for 2 months. The function of the parotid and submandibular glands was then determined by pilocarpine-stimulated salivary secretion. A 45% decrease in the function of both glands was obtained when compared to nonirradiated controls. Treatment prior to irradiation (90 min) with cyclocytidine (200 mg/kg) led to a massive degranulation of the parotid gland and yielded nearly complete protection from radiation-induced damage. In contrast, pilocarpine stimulation prior to irradiation led to a marginal degranulation of the parotid gland and yielded only 13% protection. Neither agent caused degranulation of the submandibular gland mucous cells or yielded functional protection of this gland. Treatment with both agents yielded a marked increase in iron, copper and manganese levels in the parotid gland saliva. An analogous marked increase in the redox activity of iron and copper ions was recorded for the parotid saliva stimulated by pilocarpine and cyclocytidine. Pilocarpine-stimulated submandibular gland saliva contained metal levels similar to those of the parotid gland saliva. However, no redox activity and no increase in metal mobilization could be demonstrated in the submandibular gland saliva stimulated by both agents. The correlation between the patterns of gland degranulation, mobilization of redoxactive metals and the protection of gland function, for both parotid and submandibular glands, focuses attention on the catalytic roles played by transition metal ions in promoting free radical reactions, which likely participate in the process of injury to the tissue.

Ancitabine↗

PubMed1996

Inhibition of purified soluble guanylyl cyclase by copper ions.

The aim of the present study was to investigate the effect of Cu(II) ions on soluble guanylyl cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2; sGC] and to test for a possible physiological role of this putative cofactor of the enzyme [Gerzer et al., FEBS Lett. 132: 71-74, 1981]. CuSO4 was found to inhibit NO-stimulated 5GC with an IC50 of 2.2 +/- 0.3 microM. Virtually complete inhibition of guanosine-3',5'-cyclic monophosphate (cGMP) formation was observed at 10 microM of the copper salt. Presence of CuSO4 (2 microM) did not significantly affect the potency of 2,2-diethyl-1-nitroso-oxyhydrazine (DEA/NO) but did markedly decrease maximal cyclase activity from 3.71 +/- 0.2 mumol cGMP x mg-1 x min-1 to 1.75 +/- 0.2 mumol cGMP x mg-1 x min-1. The nonstimulated enzyme was also sensitive to CuSO4 (IC50 of 6.2 +/- 1.2 microM). Addition of glutathione, which potently complexes Cu(I) ions, induced a pronounced rightward shift of the concentration-response curves for inhibition by CuSO4 of both DEA/NO-stimulated and nonstimulated guanylyl cyclase. The inhibitory effect of CuSO4 was completely antagonized by the specific Cu(I) chelator neocuproine, with a half-maximal effect at 5.9 +/- 0.2 microM. In contrast, the Cu(II) chelator cuprizone and several thiols, which do not form stable Cu(I) complexes, were far less protective. Our results suggest that inhibition of soluble guanylyl cyclase by CuSO4 is unrelated to heme-mediated enzyme stimulation and may arise from the reversible high affinity binding of Cu(I) ions to a site of the protein that is critically involved in enzyme catalysis.

Animals↗

PubMed1996

Increased levels of redox-active iron in follicular fluid: a possible cause of free radical-mediated infertility in beta-thalassemia major.

OBJECTIVE: Our purpose was to investigate the follicular fluid parameters associated with redox activity and the consequent production of the deleterious hydroxyl radical in beta-thalassemia major. STUDY DESIGN: The levels of ferritin, total iron, total copper, and redox-active iron were measured in follicular fluid aspirated from three follicles during three consecutive ovum pickups from a patient with beta-thalassemia major and were compared with the levels in nine follicles aspirates from nine healthy control patients. The redox activity in the follicular fluid samples was monitored by the extent of follicular fluid-mediated deoxyribonucleic acid degradation and salicylate hydroxylation. RESULTS: Total iron and ferritin concentrations were elevated in thalassemic follicular fluid samples compared with control samples (6.7 fold, and 53.3-fold, respectively), whereas the total copper concentration was similar. Thalassemic follicular fluid samples exhibited a marked increase of redox activity, indicating a higher potential of free radical production leading to deoxyribonucleic acid degradation. Likewise, free radical-induced conversion of salicylate to dihydroxybenzoic acid derivatives was enhanced in the thalassemic follicular fluid samples compared with controls (2,3-dihydroxybenzoic acid: 67.7 +/- 22 vs 20.3 +/- 12.9 ng/mg protein; 2,5-dihydroxybenzoic acid: 101.6 +/- 25.9 vs 4.42 +/- 2.7 ng/mg protein). CONCLUSIONS: The increased level of redox activity found in the follicular fluid from a patient with beta-thalassemia major focuses the attention on the small fraction of redox-active iron ions as mediators of free radical production, inducing tissue injury and possibly contributing to impairment of reproduction in these patients.

Adult↗

PubMed1995

The role of iron in beta amyloid toxicity.

There is evidence that oxidative damage plays a causative role in Alzheimer's disease and amyloid beta protein (A beta) toxicity. Iron is frequently a potent facilitator of free radical production due to its ability to mediate the conversion of H2O2 to hydroxyl radicals via the Fenton reaction or by virtue of hypervalent iron compounds. It is shown here that iron facilitates A beta toxicity to cultured cells.

Alzheimer Disease↗

PubMed1995

Hydroxyl radical generation in beta-thalassemic red blood cells.

To provide more experimental evidence for the proposed role of oxygen free radicals in red blood cell (RBC) damage in beta-thalassemia, hydroxyl radical generation was studied in thalassemic (Th) vs. normal (N) RBC. .OH fluxes were quantified by the conversion of salicylic acid (SA) into its hydroxylated products, 2,3- and 2,5-dihydroxybenzoic acids (DHBA) and catechol, assayed with HPLC coupled to electrochemical detection. No significant difference in spontaneous .OH generation between N-RBC and Th-RBC was found. Ascorbic acid (0.5-3.0 mM) induced many-fold increases in SA hydroxylation in a dose-dependent manner in both types of cells. In the presence of ascorbate (1.0 mM), the SA hydroxylated products were determined in Th-RBC vs. N-RBC as follows (nmol/ml): 2,5-DHBA, 1.45 +/- 0.06 vs. 1.81 +/- 0.05 (p = 0.001); 2,3-DHBA, 1.89 +/- 0.21 vs. 1.15 +/- 0.08 (p = 0.008) and catechol, 0.87 +/- 0.13 vs. 0.38 +/- 0.05 (p = 0.006). The results showed significant increase in the total SA hydroxylation in Th-RBC as compared to N-RBC with a tendency to form 2,3-DHBA and catechol at the expanse of 2,5-DHBA. The excessive .OH generation in Th-RBC is attributed to the abnormally high content of redox active iron in the cytosolic and/or membrane compartments of these cells.

Catechols↗

PubMed1995

Effects of zinc-desferrioxamine on Plasmodium falciparum in culture.

The zinc-desferrioxamine (Zn-DFO) complex is considered to be more permeative into parasitized erythrocytes than is the metal-free DFO. The former may penetrate the cell and exchange its bound zinc for ferric ions, rendering the iron unavailable for vital parasite functions. The effects of these compounds on the in vitro development of Plasmodium falciparum are compared. The results indicate that Zn-DFO is superior to DFO, especially at concentrations below 20 microM, as shown by decreased levels of hypoxanthine incorporation, lower levels of parasitemia, and interference with the life cycle of the parasite. At low concentrations, DFO even enhanced parasite growth. Such an enhancement was not observed following exposure to Zn-DFO. Experiments in which the compounds were removed from the cultures indicated that parasites treated with Zn-DFO are less likely to recover at a later stage. Since DFO has already been used in humans for the treatment of malaria, its complex with zinc, which is more effective in vitro, should also be examined in vivo.

Animals↗

PubMed1993

Copper and iron are mobilized following myocardial ischemia: possible predictive criteria for tissue injury.

Direct evidence for substantial mobilization of copper in the coronary flow immediately following prolonged, but not short, cardiac ischemia is presented. In the first coronary flow fraction (CFF) of reperfusion (0.15 ml), after 35 min of ischemia, the level of copper (as well as of iron) was 8- to 9-fold higher than the preischemic value. The levels in subsequent CFFs decreased and reached the preischemic value, indicating that both metals appear in a burst at the resumption of coronary flow. When the first CFF was used in a reaction mixture containing ascorbate and salicylate, the latter underwent chemical hydroxylation and was converted to its dihydroxybenzoate derivatives. Likewise, this CFF promoted the ascorbate-driven DNA degradation. Subsequent 150 CFFs were serially collected and demonstrated low activities. Following 18 min of ischemia, the copper level in the first CFF of reperfusion was only 15% over the preischemic value. In contrast, the mobilization of iron into coronary flow was significant but markedly lower than after 35 min. The levels of copper and the redox activity of the first CFF correlated well with the degree of loss of cardiac function, after 18 and 35 min of ischemia, respectively. After 18 min of ischemia, cardiac function was about 50% and the damage is considered reversible, whereas after 35 min the functional loss exceeded 80% and is considered irreversible. These results are in accord with the causative role that copper and iron can play in heart injury following ischemia, by virtue of their capacity to catalyze the production of hydroxyl radicals, and could lead to the development of new modalities for intervention in tissue injury.

Animals↗

PubMed1993

Hydroxyl radical generation in the cat retina during reperfusion following ischemia.

There is increasing evidence that oxygen-derived free radicals are generated during the early phase of reperfusion, and account for part of the damage caused by transient ischemia in various tissues. To study this in the retina, cats were injected intravenously with sodium salicylate (100 mg kg-1), which reacts as a hydroxyl radical trap to form 2,3- and 2,5-dihydroxybenzoic acids (DHBA). Thirty minutes following injection, the retina of one eye of each animal was subjected to ischemia by intraocular pressure elevation via cannulation of the anterior chamber, while the fellow eye served as a sham-operated control. Ischemia was induced for 60 min (six eyes) and 90 min (eight eyes) followed by 5 min of reperfusion. In six other eyes, ischemia was induced for 90 min without reperfusion. After enucleation, the retinas were immediately removed, placed in ice-cold buffer and the retinal levels of 2,3- and 2,5-DHBA were quantitated by high pressure liquid chromatography, coupled with electrochemical detection. Results were normalized and expressed as ng DHBA microgram-1 salicylate mg-1 retinal protein. After 60 min of ischemia followed by reperfusion the normalized levels of 2,3- and 2-5-DHBA were no different in the experimental and control retinas. However, the levels of both 2,3- and 2,5-DHBA were significantly higher in the retinas subjected to 90 min ischemia followed by reperfusion than in the control tissues (P = 0.012 and P = 0.036, n = 8 respectively). Following 90 min ischemia without reperfusion, the normalized dihydroxybenzoate levels in the retinas were no higher than in their controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Is hemin responsible for the susceptibility of Plasmodia to oxidant stress?

Based on the unusually high and stage-dependent susceptibility of Plasmodia to oxidant stress it has been proposed that during parasite development, increasing levels of redox-active forms of iron are gradually released. The purpose of this study was to examine this proposal by using an assay monitoring the levels of available forms of iron for redox reactions. Ascorbate-driven and iron-mediated degradation of adventitious DNA served as the basis for this functional assay. Incubation of DNA with lysate from infected RBC caused massive degradation, which was dose, time- and parasite-stage dependent. In contrast, lysate from non-infected RBC did not induce DNA degradation. Likewise, lysate only from infected RBC enhanced the aerobic oxidation of ascorbate. These effects on both reaction, DNA degradation and ascorbate oxidation, could be reconstructed with hemin, instead of lysate. Also, chelators exerted similar effects on both reactions. The results suggest that increased levels of redox-active forms of iron are liberated during parasite development. We propose that hemin or hemin-like structures are the appropriate candidates which could catalyze oxidative stress and deregulate the delicate redox balance of the host-parasite system.

Animals↗

PubMed1993

Interaction between allopurinol and copper: possible role in myocardial protection.

Allopurinol, a potent inhibitor of xanthine oxidase, is known to effectively protect the heart against damage in patients undergoing cardiac bypass surgery. There is still an ambiguity concerning the presence of xanthine oxidase in the human heart. Thus, the mechanism underlying the protective effect of allopurinol is unclear. Transition metal ions, such as iron and copper, can participate in single-electron reactions and mediate the formation of oxygen-derived free radicals. In this study the interaction between allopurinol and Cu(II) was investigated. Spectrophotometric investigation shows that allopurinol (0-0.8 mM) form a 1:1 complex with Cu(II) ions (0-0.8 mM) with a specific absorbance peak at 364 nm. Also, the rate constant (k) for the copper-catalyzed aerobic oxidation of ascorbate was markedly decreased in the presence of allopurinol (from 0.068 min-1 to 0.014 min-1). Allopurinol substantially reduced the copper-mediated and ascorbate-driven DNA breakage. Spectrophotometric measurements did not indicate a specific interaction between iron ions and allopurinol. It is suggested that the beneficial effects of allopurinol during reperfusion of the heart could stem from its chelation of copper, yielding a complex with low redox activity.

Allopurinol↗

PubMed1992

Effects of N'methyl-N'-nitro-N-nitrosoguanidine and deoxycholic acid on the content of free radicals in rat serum.

The aim of this study was to determine whether changes in serum free radicals may be useful for the early detection of precancerous conditions in the rat colon after treatment with a direct carcinogen (N-Methyl-N'-Nitro-N-Nitrosoguanidine, MNNG) and a secondary bile acid (deoxycholic acid, DCA) as a tumor promoter. It was shown that a significant increase in the concentrations of free radicals in sera of rats following their treatment with MNNG and DCA was observed as early as the 18th week after the beginning of the treatment. Since our results have shown that these alterations occurred in parallel with neoplastic transformations in the rat colon, it suggests that the increase in serum free radicals reflected the precancerous situation in the animals and may be useful in the early detection of cancer development. The possible role of free radicals in deoxycholate-induced liver toxicity was discussed.

Animals↗