62 research outputs found
Protection of mitochondria during cold storage of liver and following transplantation: comparison of the two solutions, University of Wisconsin and Eurocollins
Abstract Injury to allografts during ischaemia/reperfusion
contribute to the development of graft failure following transplantation
with significant morbidity and mortality to patients.
The development of University ofWisconsin solution
has significantly improved the quality of graft preservation
and transplant outcome relative to formerly used solutions
such as Eurocollins. The aim of this study was to further
characterize mitochondrial structural and functional alterations
occurring in rat livers following cold storage and
transplantation. Mitochondrial impairment after prolonged
storage in Eurocollins included decreased cyt. c+c1, cyt. b
and cyt. a+a3 concentration and dramatic falls in the activities
of the respiratory chain enzymes ubiquinol-cyt. c
oxidoreductase and cytochrome oxidase. Under the same
conditions the highest hydroperoxide but lowest vitamin E
concentrations were also found. Although both the Eurocollins
and University of Wisconsin preservation solutions
have limitations in preventing oxidative injuries following
cold storage and reperfusion, our data indicate that mitochondrial
impairment was higher in Eurocollins- than
in University of Wisconsin-stored livers. Further improvements
are necessary in maintaining the stability of mitochondria
in order to optimize preservations solutions used in
transplantations
Protection of Polyphenols against Glyco-Oxidative Stress: Involvement of Glyoxalase Pathway
Chronic high glucose (HG) exposure increases methylglyoxal (MGO)-derived advanced glycation end-products (AGEs) and is involved in the onset of pathological conditions, such as diabetes, atherosclerosis and chronic-degenerative diseases. Under physiologic conditions the harmful effects of MGO are contrasted by glyoxalase system that is implicated in the detoxification of Reactive Carbonyl Species (RCS) and maintain the homeostasis of the redox environment of the cell. Polyphenols are the most abundant antioxidants in the diet and present various health benefits. Aims of the study were to investigate the effects of HG-chronic exposure on glyco-oxidation and glyoxalase system in intestinal cells, using CaCo-2 cells. Moreover, we studied the effect of apple polyphenols on glyco-oxidative stress. Our data demonstrated that HG-treatment triggers glyco-oxidation stress with a significant increase in intracellular Reactive Oxygen Species (ROS), lipid peroxidation, AGEs, and increase of Glyoxalase I (GlxI) activity. On the contrary, Glyoxalase II (GlxII) activity was lower in HG-treated cells. We demonstrate that apple polyphenols exert a protective effect against oxidative stress and dicarbonyl stress. The increase of total antioxidant capacity and glutathione (GSH) levels in HG-treated cells in the presence of apple polyphenols was associated with a decrease of GlxI activity
Side Effects of Curcumin: Epigenetic and Antiproliferative Implications for Normal Dermal Fibroblast and Breast Cancer Cells
Curcumin is a yellow-orange pigment obtained from the plant Curcuma longa, which is known to exert beneficial effects in several diseases, including cancer. However, at high doses, it may produce toxic and carcinogenic effects in normal cells. In this context, we studied the effects of curcumin on normal human dermal fibroblast (HDF) cells and breast cancer cells (MCF7)
Lack of in vitro protection by a common sunscreen ingredient on UVA-induced cytotoxicity in keratinocytes
As an extension of our previous investigations on sunscreen ingredients, the present work was aimed at assessing the possible
protective effects of a common UVA-absorbing agent, Parsol 1789 (4-tert-butyl-4-methoxydibenzoylmethane) in contact with
human keratinocytes under UVA illumination. Cell viability was evaluated by determining lactate dehydrogenase (LDH) release,
uptake of propidium iodide and fluorescein diacetate, total protein content and percentage of cell detachment. Apoptosis was
detected by recognition of translocated phosphatidylserine using annexin V-FITC uptake. Oxidative stress was evaluated through
the carboxy-H2DCFDA assay while the total oxyradical scavenging capacity (TOSC) assay was used for determining the total
antioxidant capacity level in these cells. Lipid peroxidation was also assessed by checking hydroperoxide (HP) levels. The
results obtained show that UVA exposure induces significant cell mortality, decrease in protein concentration, release of LDH,
increase in apoptosis, oxidative stress and lipid peroxidation with a concomitant reduction in the response of the antioxidant
cellular defense system. The presence of 10M Parsol 1789 did not minimize these UVA-induced effects, on the contrary,
for some parameters measured such as lipid hydroperoxides, there was a significant enhancement. Furthermore, the presence
of glutathione (GSH) alone decreased the level of ROS and lipid hydroperoxides, but in combination with Parsol 1789, this
protective effect was reduced. The overall results indicate that the compound does not protect these cells from UVA exposure
under our experimental conditions confirming previous findings on the lack of photoprotective efficiency of this sunscreen in
contact with biologically relevant molecules. However, the biological role and significance of these results to the consequences
of sunscreen use in humans are not known, hence extrapolation from laboratory experiments must be done with caution.
© 2004 Elsevier Ireland Ltd. All rights reserved
Placebo-controlled double-blind randomized trial on the use of L-carnitine, L-acetylcarnitine, or combined L-carnitine and L-acetylcarnitine in men with idiopathic asthenozoospermia
Objective: To evaluate the effectiveness of L-carnitine (LC) or L-acetyl-carnitine (LAC) or combined LC and LAC treatment in improving semen kinetic parameters and the total oxyradical scavenging capacity in semen. Design: Placebo-controlled, double-blind, randomized trial.Setting: Andrology unit, Department of Internal Medicine, Polytechnic University of Marche, Italy.Patient(s): Sixty infertile men, ages 20 to 40 years, with the following baseline sperm selection criteria: concentration > 20 × 10 6 / mL, sperm forward motility < 50 %, and normal sperm morphology > 30 %; 59 patients completed the study.Intervention(s): Patients underwent a double-blind therapy of LC 3 g / d, LAC 3 g / d, a combination of LC 2 g / d + LAC 1 g / d, or placebo. The study design was 1 month of run in, 6 months of therapy or placebo, and 3 months of follow-up evaluation.Main Outcome Measure(s): Variations in semen parameters used for patient selection, and variations in total oxyradical scavenging capacity of the seminal fluid.Result(s): Sperm cell motility (total and forward, including kinetic features determined by computer-assisted sperm analysis) increased in patients to whom LAC was administered both alone or in combination with LC; combined LC + LAC therapy led to a significant improvement of straight progressive velocity after 3 months. The total oxyradical scavenging capacity of the semen toward hydroxyl and peroxyl radicals also increased and was positively correlated with the improvement of kinetic features. Patients with lower baseline values of motility and total oxyradical scavenging capacity of the seminal fluid had a significantly higher probability of responding to the treatment.Conclusion(s): The administration of LC and LAC is effective in increasing sperm kinetic features in patients affected by idiopathic asthenozoospemia and improves the total oxyradical scavenging capacity of the seminal fluid in the same population (Fertil Steril ® 2005;84:662–71.©2005 by American Society for Reproductive Medicine.).</p
Interplay among Oxidative Stress, Methylglyoxal Pathway and S-Glutathionylation
Reactive oxygen species (ROS) are produced constantly inside the cells as a consequence of nutrient catabolism. The balance between ROS production and elimination allows to maintain cell redox homeostasis and biological functions, avoiding the occurrence of oxidative distress causing irreversible oxidative damages. A fundamental player in this fine balance is reduced glutathione (GSH), required for the scavenging of ROS as well as of the reactive 2-oxoaldehydes methylglyoxal (MGO). MGO is a cytotoxic compound formed constitutively as byproduct of nutrient catabolism, and in particular of glycolysis, detoxified in a GSH-dependent manner by the glyoxalase pathway consisting in glyoxalase I and glyoxalase II reactions. A physiological increase in ROS production (oxidative eustress, OxeS) is promptly signaled by the decrease of cellular GSH/GSSG ratio which can induce the reversible S-glutathionylation of key proteins aimed at restoring the redox balance. An increase in MGO level also occurs under oxidative stress (OxS) conditions probably due to several events among which the decrease in GSH level and/or the bottleneck of glycolysis caused by the reversible S-glutathionylation and inhibition of glyceraldehyde-3-phosphate dehydrogenase. In the present review, it is shown how MGO can play a role as a stress signaling molecule in response to OxeS, contributing to the coordination of cell metabolism with gene expression by the glycation of specific proteins. Moreover, it is highlighted how the products of MGO metabolism, S-D-lactoylglutathione (SLG) and D-lactate, which can be taken up and metabolized by mitochondria, could play important roles in cell response to OxS, contributing to cytosol-mitochondria crosstalk, cytosolic and mitochondrial GSH pools, energy production, and the restoration of the GSH/GSSG ratio. The role for SLG and glyoxalase II in the regulation of protein function through S-glutathionylation under OxS conditions is also discussed. Overall, the data reported here stress the need for further studies aimed at understanding what role the evolutionary-conserved MGO formation and metabolism can play in cell signaling and response to OxS conditions, the aberration of which may importantly contribute to the pathogenesis of diseases associated to elevated OxS
Reaction of endogenous Coenzyme Q(10) with nitrogen monoxide and its metabolite nitrogen dioxide
WOS:000477607500001Objectives: Coenzyme Q(10), incorporated in DOPC lyposomes or naturally present in liver bovine mitochondria or in human blood plasma, was reacted with nitrogen dioxide (NO2)-N-center dot or with a (NO)-N-center dot/(NO2)-N-center dot mixture. Methods and Results: The reaction course was monitored by Electron Paramagnetic Resonance (EPR) spectroscopy and in all cases the formation of a di-tert-alkyl nitroxide was observed, deriving from the addition of (NO2)-N-center dot to one of the double bonds, most likely the terminal one, of the isoprenic chain. The rate constant for nitroxide formation was also determined by EPR spectroscopy and an initial rate of ca. 7 x 10(-8 )M s(-1) was obtained
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