Protective effect of PEG 35,000 Da on renal cells: paradoxical activation of JNK signaling pathway during cold storage.

Polyethylene glycol (PEG), a high-molecular weight colloid, is added to preservation solutions in order to decrease cold- and ischemia-induced injuries of the grafted organ. We evaluated on LLC-PK1, a porcine proximal tubular epithelial cell line (1) the efficiency of several commercial preservation solutions (University of Wisconsin, Euro-Collins, Celsior, SCOT, IGL-1), and (2) whether adding PEG (400-35,000 Da) in a simple extracellular-type buffer modified cell integrity and mitogen-activated protein kinase (MAPK) signaling pathways. SCOT was the most efficient commercial solution.

Cyclooxygenase 1-dependent production of F2-isoprostane and changes in redox status during warm renal ischemia-reperfusion.

The detrimental role of oxidative stress has been widely described in tissue damage caused by ischemia-reperfusion. A nonenzymatic, reactive oxygen species-related pathway has been suggested to produce 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)), an epimer of prostaglandin F(2alpha) (PGF(2alpha)), which has been proposed as an indicator of oxidative stress. Using an in vivo ischemia-reperfusion model in rat kidneys, we investigated intrarenal accumulation of 8-iso-PGF(2alpha) and PGF(2alpha).

Evidence for a protective role of trimetazidine during cold ischemia: targeting inflammation and nephron mass.

Ischemia-reperfusion injury (IRI) is associated with an increased risk of acute rejection, delayed graft function, or chronic graft dysfunction. Mitochondria plays a central role in this process. Using an autotransplant pig kidney model, changes in renal function and morphology were determined after different periods of cold ischemia in kidneys preserved in the University of Wisconsin solution (UW), high-Na(+) version of UW (HEH) or Celsior (CEL) a newly developed high-Na(+) solution, with or without trimetazidine (TMZ).

Plasmalogen degradation by oxidative stress: production and disappearance of specific fatty aldehydes and fatty alpha-hydroxyaldehydes.

Plasmalogens are often considered as antioxidant molecules that protect cells from oxidative stress. Their vinyl ether bond could indeed be among the first targets for newly formed radicals. However, the long chain aldehydes released from plasmalogens were seldom studied and possible injurious or harmless effects were poorly examined.

Evidence against a major role of plasmalogens in the resistance of astrocytes in lactic acid-induced oxidative stress in vitro.

Astrocytes are known to play a key role in buffering extracellular pH variations and, in addition, they are particularly resistant to oxidative stress and subsequent lipid peroxidation. This great resistance may be ascribed to the presence of high concentrations of certain antioxidants, but another explanation may be the presence of a high quantity of plasmalogens, which are a special group of glycerophospholipids characterized by a vinyl ether bond instead of an ester bond in the sn-1 position of the glycerol backbone. Plasmalogens are sensitive to free radical attack and acidity, and numerous works have supported the hypothesis that they may be antioxidant molecules that protect cells from oxidative stress.

Age-related changes in ethanolamine glycerophospholipid fatty acid levels in rat frontal cortex and hippocampus.

Morphological and biochemical alterations are associated with a progressive age-related cognitive deficit. Plasmenylethanolamine, the major brain plasmalogen, may be modified during aging because of a possible antioxidant role and involvement in synaptic transmission. Two- and 18-month-old rats were used to study the effect of aging on the levels and acyl composition of plasmenylethanolamine (PmE), phosphatidylethanolamine (PE), and phosphatidylserine (PS) in the frontal cortex and hippocampus.

Quantification of long-chain aldehydes by gas chromatography coupled to mass spectrometry as a tool for simultaneous measurement of plasmalogens and their aldehydic breakdown products.

The cleavage of the specific vinyl ether linkage at the sn-1 position of plasmalogens leads to the formation of two products: the 1-lyso-2-acyl glycerophospholipid and a long-chain fatty aldehyde. Plasmalogens are measured by quantifying one of these two products. In this paper, we describe a rapid and sensitive procedure for measuring plasmalogens via quantification of long-chain fatty aldehydes.

Pharmacological limitation of damage to renal medulla after cold storage and transplantation by trimetazidine.

Delayed graft function remains an important complication after renal transplantation. In this study, we investigated the influence of trimetazidine (TMZ), a cytoprotective agent, on renal medullary damage after prolonged preservation and autotransplantation. Pig kidneys were cold-flushed and preserved (48 h at 4 degrees C) with two standard renal preservation solutions Euro-Collins and University of Wisconsin supplemented or not with TMZ (10(-6) M).

Early evaluation of renal reperfusion injury after prolonged cold storage using proton nuclear magnetic resonance spectroscopy.

Background: Proton nuclear magnetic resonance (NMR) spectroscopy can be used as a non-invasive tool to measure renal damage. In the present investigation, proton NMR spectroscopy of urine was assessed in order to detect cellular damage after different periods of cold ischaemia in two standard preservation solutions.

Methods: The isolated perfused pig kidney was used to assess initial renal function after in situ cold flush and cold storage (CS) for 24 or 48 h in two standard preservation solutions: EuroCollins (EC) and University of Wisconsin (UW) solutions.

Lactic acid-induced increase of extracellular dopamine measured by microdialysis in rat striatum: evidence for glutamatergic and oxidative mechanisms.

Striatal lactacidosis was induced by direct lactic acid perfusion to obtain a local pH as close as possible to that observed in ischemia. In a previous study we showed that such lactacidosis produces a diphasic increase in extracellular dopamine (DA). The present work investigated whether DA accumulation is related to a glutamatergic mechanism and/or production of reactive oxygen species (ROS) in the striatum.

Effects of 4-hydroxynonenal, a lipid peroxidation product, on dopamine transport and Na+/K+ ATPase in rat striatal synaptosomes.

Incubation of rat striatal synaptosomes in ascorbic acid induced the production of thiobarbituric acid reactive substances, a marker of lipid peroxidation, and 4-hydroxynonenal (4-HNE), a lipid peroxidation aldehydic product. Incubations with 4-HNE, used at a range of concentrations comparable to those obtained during peroxidation, induced a simultaneous, dose-dependent decrease of dopamine (DA) uptake and Na+/K+ ATPase activity and a loss of sulfhydryl (SH) groups. Similar results were observed in a previous study when lipid peroxidation was induced after incubation of synaptosomes in ascorbic acid.

Membrane carbohydrate conjugates desialylation does not alter [3H]-dopamine uptake in rat striatal slices.

Incubation of rat striatal slices induced a large decrease (about 50%) of DA uptake and a slight desialylation of polysialogangliosides (GT1b, GD1b, GD1a) with an increase of monosialogangliosides (GM1). Moreover, a pretreatment of slices by exogenous added neuraminidase of Vibrio cholerae did not modify DA uptake, although the pattern of gangliosides was modified and there was considerable loss (about 45%) of sialic acid in gangliosides and glycoproteins. It was verified that neuraminidase activity occured in synaptic membrane.

Efficiency of trimetazidine in renal dysfunction secondary to cold ischemia-reperfusion injury: a proposed addition to University of Wisconsin solution.

Nonspecific injury in cadaveric renal transplants adversely affects early graft function and influences long-term graft survival after organ transplantation. Trimetazidine (TMZ) has been reported to exert a protective action against normothermic ischemia and reperfusion injury in several experimental and clinical studies. In an isolated perfused pig kidney model, we investigated the effects of TMZ added to University of Wisconsin solution (UW) during 48 or 72 h of cold storage (CS) and the consequence during reperfusion.

Autoxidation of rat brain homogenate: evidence for spontaneous lipid peroxidation. Comparison with the characteristics of Fe2+- and ascorbic acid-stimulated lipid peroxidation.

Aerobically-incubated brain homogenates are known to undergo autoxidation characterized by spontaneous TBARS production, presumably as a result of lipid peroxidation. However, TBARS measurement alone, because of its lack of specificity, is not sufficient to demonstrate the occurrence of lipid peroxidation in complex biological systems. This study, undertaken to determine whether or not spontaneous oxidation of rat brain homogenate is due to lipid peroxidation, measured different specific markers of this process (fatty acids, lipid aldehydes and the formation of fluorescence products) and studied changes in alpha-tocopherol.

Chronic dietary n-3 polyunsaturated fatty acids deficiency affects the fatty acid composition of plasmenylethanolamine and phosphatidylethanolamine differently in rat frontal cortex, striatum, and cerebellum.

As chronic consumption of a diet devoid of n-3 fatty acid induced modification of neurotransmission pathways in the frontal cortex of rats, plasmalogen alteration could occur in this area. Because of the propensity to facilitate membrane fusion, plasmenylethanolamine (PmE), a major plasmalogen of brain, may be involved in synaptic transmission. Female rats were fed diet containing peanut oil [(n-3)-deficient diet] through two generations.

Changes in excitatory amino acid levels and tissue energy metabolites of neonate rat brain after hypoxia and hypoxia-ischemia.

Lactate accumulation, amino acid aspartate and glutamate levels, and hypoxanthine, xanthine and malondialdehyde (MDA) concentrations were compared in neonate rat brain after transient global hypoxia induced alone or in association with unilateral ligation of a carotid artery. Lactate production in both hemispheres was higher in cerebral hypoxia-ischemia (CHI) than in cerebral hypoxia (CH), and was lower in CHI after 2 h than at 15 min of recovery. Aspartate and glutamate levels were reduced 15 min after CHI in both hemispheres, but aspartate alone was decreased 2 h after CHI in the ipsilateral (left) hemisphere and 15 min after CH in both hemispheres.

MPTP toxicity in rat striatal slices: dopamine uptake alteration does not appear to be related to lipid peroxidation.

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which is used to create experimental models of parkinsonism, induces both dopaminergic neurotoxicity and peroxidation reactions. The present work investigated the interaction between the dopamine (DA) uptake system, lipid peroxidation and MPTP in a rat striatum slice model. [3H]DA uptake was decreased and the concentration of thiobarbituric acid reactive substances (TBARS) increased after a plain preincubation in Krebs-Ringer bicarbonate buffer for 150 min.

Alterations in the ganglioside composition of rat cortical brain slices during experimental lactic acidosis: implications of an enzymatic process independent of the oxidative stress.

Several in vitro studies have shown that lactic acidosis plays a role in brain damage by enhancing free radical formation and lipid peroxidation. The purpose of this study was to determine whether gangliosides are affected by lactic acid-induced oxidation in rat brain tissues. Cortical brain slices were incubated at 37 degrees C for 5 or 17 h in Krebs-Ringer buffer containing 20 mM lactic acid (final pH 5.

Gentamicin-induced kidney damage and lipid peroxidation in rats.

Although it has been reported that injections of gentamicin induces lipid peroxidation in rat renal cortex (Ramsammy et al. (1985) Biochem. Pharmacol.

[Auto-oxidation or brain homogenate: research of oxidizing agent and targets. Comparison with liver homogenate].

The aim of this study was to determine: 1) the source of Thiobarbituric Reactive Substances (TBARS) spontaneously produced during rat brain homogenate incubation; 2) the cellular components involved; 3) the reason why brain and liver homogenates did not have the same behaviour. Measurements of TBARS, Polyunsaturated Fatty Acids (PUFAs), aldehydes coming from PUFAS breakdown, vitamin E and Schiff's bases levels were performed on brain and liver homogenates, membrane fractions (Mb) and medium containing soluble cytoplasmic components (CS). Mb and CS were prepared by differential centrifugation.

Lack of correlation between TBARS production and PUFA degradation during incubation of membrane erythrocytes in an OH. (Fe2+/H2O2) generator system.

We investigated the effects of an OH. (Fe2+/H2O2) generator system on erythrocyte membrane, particularly the time-course of lipid peroxidation as estimated by measurement of conjugated dienes, thiobarbituric reactive substances (TBARS), lipofuscin-like pigments, and alpha-tocopherol. Polyunsaturated fatty acids (PUFAs), especially arachidonic acid (20:4 omega 6) and docosahexenoic acid (22:6 omega 3), were also measured.