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Membrane Damage (membrane + damage)
Kinds of Membrane Damage Selected AbstractsANTI-OXIDANT MECHANISMS OF KOLAVIRON: STUDIES ON SERUM LIPOPROTEIN OXIDATION, METAL CHELATION AND OXIDATIVE MEMBRANE DAMAGE IN RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2005EO Farombi SUMMARY 1.,In the present study, we have examined the ability of kolaviron, a natural biflavonoid from Garcinia kola seeds, to prevent the susceptibility of rat serum lipoprotein to undergo oxidative modification in vitro and ex vivo. In addition, its ability to chelate metal ions and mitigate iron/ascorbate-induced damage to microsomal lipids was investigated. 2.,Lipoprotein resistance to copper-induced oxidation was highly improved in rats treated with kolaviron (100 mg/kg) for 7 days, as demonstrated by a significant increase in lag time compared with control. A significant (P < 0.05) decrease in area under the curve (AUC) and slope of propagation was observed in kolaviron-treated rats compared with control. Conjugated dienes formed after 240 min of lipoprotein oxidation were markedly decreased in kolaviron-treated rats compared with controls. Malondialdehyde concentrations were significantly reduced in the serum lipoproteins of kolaviron-treated rats with an attendant significant increase in the total anti-oxidant activity compared with control. 3.,In vitro, kolaviron (10,60 µmol/L) inhibited the Cu2+ -induced oxidation of rat serum lipoprotein in a concentration-dependent manner. Kolaviron, at 20 and 60 µmol/L, produced 48 and 87% inhibition of oxidation of lipoprotein, respectively. Compared with control, kolaviron, at 10 and 20 µmol/L, resulted in 29 and 47% decreases in AUC, respectively. In addition, kolaviron (10 µmol/L) elicited a 53% increase in lag time, whereas 40 and 60 µmol/L kolaviron produced 38 and 88% decreases in slope, respectively. 4.,Kolaviron effectively prevented microsomal lipid peroxidation induced by iron/ascorbate in a concentration-dependent manner. Kolaviron at the highest dose tested (90 µmol/L) had a significant chelating effect on Fe2+ (78%). 5.,In conclusion, our data demonstrate that kolaviron protects against the oxidation of lipoprotein, presumably by mechanisms involving metal chelation and anti-oxidant activity, and, as such, may be of importance in relation to the development of atherosclerosis. [source] Activity and mechanisms of action of selected biocidal agents on Gram-positive and -negative bacteriaJOURNAL OF APPLIED MICROBIOLOGY, Issue 2 2003S.E. Walsh Abstract Aims: This study investigates the antimicrobial activity and mode of action of two natural products, eugenol and thymol, a commonly utilized biostatic agent, triclocarban (TCC), and two surfactants, didecyldimethylammonium chloride (DDDMAC) and C10,C16 alkyldimethyl amine N -oxides (ADMAO). Methods and Results: Methods used included: determination of minimum inhibitory concentrations (MICs), lethal effect studies with suspension tests and the investigation of sub-MIC concentrations on growth of E. coli, Staph. aureus and Ps. aeruginosa using a Bioscreen microbiological analyser. Leakage of intracellular constituents and the effects of potentiating agents were also investigated. Only DDDMAC was bactericidal against all of the organisms tested. Eugenol, thymol and ADMAO showed bacteriostatic and bactericidal activity, but not against Ps. aeruginosa. TCC was only bacteristatic against Staph. aureus, but like the other agents, it did affect the growth of the other organisms in the Bioscreen experiments. All of the antimicrobial agents tested were potentiated by the permeabilizers to some extent and leakage of potassium was seen with all of the agents except TCC. Conclusions: DDDMAC was bactericidal against all organisms tested and all compounds had some bacteriostatic action. Low level static effects on bacterial growth were seen with sub-MIC concentrations. Membrane damage may account for at least part of the mode of action of thymol, eugenol, DDDMAC and ADMAO. Significance and Impact of the Study: The ingredients evaluated demonstrated a range of bactericidal and bacteriostatic properties against the Gram-negative and -positive organisms evaluated and the membrane (leakage of intracellular components) was implicated in the mode of action for most (except TCC). Sub-MIC levels of all ingredients did induce subtle effects on the organisms which impacted bacterial growth, even for those which had no true inhibitory effects. [source] Cytotoxicity of lavender oil and its major components to human skin cellsCELL PROLIFERATION, Issue 3 2004A. Prashar Concerns are building about the potential for irritant or allergenic skin reactions with the use of lavender oil. This study has demonstrated that lavender oil is cytotoxic to human skin cells in vitro (endothelial cells and fibroblasts) at a concentration of 0.25% (v/v) in all cell types tested (HMEC-1, HNDF and 153BR). The major components of the oil, linalyl acetate and linalool, were also assayed under similar conditions for their cytotoxicity. The activity of linalool reflected that of the whole oil, indicating that linalool may be the active component of lavender oil. Linalyl acetate cytotoxicity was higher than that of the oil itself, suggesting suppression of its activity by an unknown factor in the oil. Membrane damage is proposed as the possible mechanism of action. [source] Alcoholic skeletal muscle myopathy: definitions, features, contribution of neuropathy, impact and diagnosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2001V. R. Preedy Alcohol misusers frequently have difficulties in gait, and various muscle symptoms such as cramps, local pain and reduced muscle mass. These symptoms are common in alcoholic patients and have previously been ascribed as neuropathological in origin. However, biochemical lesions and/or the presence of a defined myopathy occur in alcoholics as a direct consequence of alcohol misuse. The myopathy occurs independently of peripheral neuropathy, malnutrition and overt liver disease. Chronic alcoholic myopathy is characterized by selective atrophy of Type II fibres and the entire muscle mass may be reduced by up to 30%. This myopathy is arguably the most prevalent skeletal muscle disorder in the Western Hemisphere and occurs in approximately 50% of alcohol misusers. Alcohol and acetaldehyde are potent inhibitors of muscle protein synthesis, and both contractile and non-contractile proteins are affected by acute and chronic alcohol dosage. Muscle RNA is also reduced by mechanisms involving increased RNase activities. In general, muscle protease activities are either reduced or unaltered, although markers of muscle membrane damage are increased which may be related to injury by reactive oxygen species. This supposition is supported by the observation that in the UK, , -tocopherol status is poor in myopathic alcoholics. Reduced , -tocopherol may pre-dispose the muscle to metabolic injury. However, experimental , -tocopherol supplementation is ineffective in preventing ethanol-induced lesions in muscle as defined by reduced rates of protein synthesis and in Spanish alcoholics with myopathy, there is no evidence of impaired , -tocopherol status. In conclusion, by a complex series of mechanisms, alcohol adversely affects skeletal muscle. In addition to the mechanical changes to muscle, there are important metabolic consequences, by virtue of the fact that skeletal muscle is 40% of body mass and an important contributor to whole-body protein turnover. [source] Multifunctional host defense peptides: intracellular-targeting antimicrobial peptidesFEBS JOURNAL, Issue 22 2009Pierre Nicolas There is widespread acceptance that cationic antimicrobial peptides, apart from their membrane-permeabilizing/disrupting properties, also operate through interactions with intracellular targets, or disruption of key cellular processes. Examples of intracellular activity include inhibition of DNA and protein synthesis, inhibition of chaperone-assisted protein folding and enzymatic activity, and inhibition of cytoplasmic membrane septum formation and cell wall synthesis. The purpose of this minireview is to question some widely held views about intracellular-targeting antimicrobial peptides. In particular, I focus on the relative contributions of intracellular targeting and membrane disruption to the overall killing strategy of antimicrobial peptides, as well as on mechanisms whereby some peptides are able to translocate spontaneously across the plasma membrane. Currently, there are no more than three peptides that have been convincingly demonstrated to enter microbial cells without the involvement of stereospecific interactions with a receptor/docking molecule and, once in the cell, to interfere with cellular functions. From the limited data currently available, it seems unlikely that this property, which is isolated in particular peptide families, is also shared by the hundreds of naturally occurring antimicrobial peptides that differ in length, amino acid composition, sequence, hydrophobicity, amphipathicity, and membrane-bound conformation. Microbial cell entry and/or membrane damage associated with membrane phase/transient pore or long-lived transitions could be a feature common to intracellular-targeting antimicrobial peptides and mammalian cell-penetrating peptides that have an overrepresentation of one or two amino acids, i.e. Trp and Pro, His, or Arg. Differences in membrane lipid composition, as well as differential lipid recruitment by peptides, may provide a basis for microbial cell killing on one hand, and mammalian cell passage on the other. [source] Investigations on the Structural Damage in Human Erythrocytes Exposed to Silver, Gold, and Platinum NanoparticlesADVANCED FUNCTIONAL MATERIALS, Issue 8 2010P. V. Asharani Abstract Human erythrocytes or red blood cells (RBCs), which constitute 99% of blood cells, perform an important function of oxygen transport and can be exposed to nanoparticles (NPs) entering into the human body during therapeutical applications involving such NPs. Hence, the haemocompatibility of the Ag, Au, and Pt NPs on human RBCs is investigated. The parameters monitored include haemolysis, haemagglutination, erythrocyte sedimentation rate, membrane topography, and lipid peroxidation. The findings suggest that platinum and gold NPs are haemocompatible compared to Ag NPs. Erythrocytes exhibit significant lysis, haemagglutination, membrane damage, detrimental morphological variation, and cytoskeletal distortions following exposure to Ag NPs at a concentration of 100,µg,mL,1. Exposure of Ag+ to RBCs shows no lysis or deterioration, implying that the observed toxicity is solely due to NPs. The haemolyzed erythrocyte fraction has the ability to induce DNA damage in nucleated cells. Additionally, multiple pits and depressions are observed on RBC membrane following exposure to Ag NPs (50,µg,mL,1 onwards). Hence, it is apparent that Ag NPs exhibit toxicity on RBCs and on other cells that are exposed to NP-mediated haemolyzed fractions. [source] Potentiation of isoniazid-induced liver toxicity by rifampicin in a combinational therapy of antitubercular drugs (rifampicin, isoniazid and pyrazinamide) in Wistar rats: A toxicity profile studyHEPATOLOGY RESEARCH, Issue 10 2007Sheikh Abdullah Tasduq Aim:, Biochemical characterization of long-term toxic manifestations of anti-tubercular (anti-TB) drugs , rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) , individually and in two combinations: (i) RIF + INH, and (ii) RIF + INH + PZA in Wistar rats. Methods:, Animals received anti-TB drugs , alone or in combination , once daily p.o. for up to 90 days (doses, in mg/kg: RIF, 250; INH, 50; PZA, 100). Assays for alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin (serum) and lipid peroxidation (LPO), glutathione (GSH), glutathione peroxidase (GPx), catalase, Na+K+-ATPase and CYP 2E1 (liver) were performed to assess liver toxicity. Clinical biochemistry was done by commercial kits. Determinations were made at 0, 15, 30 and 90 days of treatment schedule. Results:, Anti-TB drugs-treated animals showed abnormal rises or falls (>1.5,2 fold) in the serum/liver parameters. Mild hyperlipidemia, hypercholesterolemia and hyperuricemia were the other pathologies. Of all the treated groups, INHalone or in combination with other drugs produced a progressive enhancement of toxicity over 15,90 days. The in vivo results were further supported by in vitro results (MTT assay, GSH and LPO) in primary cultures of rat hepatocyte. Results indicated that anti-TB drugs in combination: (i) caused membrane damage resulting in leakage of ALT, ALP and bilirubin; (ii) caused imbalance in endogenous enzymatic oxidant,antioxidant defense via increased lipid peroxidation and in glutathione homeostasis; and (iii) enhanced the CYP 2E1-mediated bioactivation mechanism. Conclusion:, Toxicity manifestations seemed to be heptocytic injury targeted at hepatocytes, bile ducts or sinusoidal cells related to hepatitis and primary biliary cholestasis. [source] Drought Tolerance in Cotton: Involvement of Non-enzymatic ROS-Scavenging CompoundsJOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 4 2009L. Yildiz-Aktas Abstract Compounds with reactive oxygen species (ROS)-scavenging ability were studied. High-performance liquid chromatography (HPLC) pattern of polyphenols, contents of proline and carotenoids, and antiradical (AR) capacity were determined. The malonyldialdehyde (MDA) level was also assessed. Tolerant and sensitive cotton genotypes were compared, grown in the Aegean region of Turkey at normal (field capacity) and limited (1/3 field capacity) water supply. Chlorogenic acid isomers and flavonoids were identified in HPLC pattern of polyphenols. At normal water supply, the tolerant genotype was distinguished by a higher content of all polyphenol types, higher proline, carotenoids and AR capacity and lower MDA level compared with the sensitive genotype. In plants subjected to water deficit, a decline of all polyphenol compounds, carotenoids and AR capacity was observed. However, this response was less pronounced in the tolerant than in the sensitive genotype, i.e. despite the stress conditions imposed, the tolerant plants maintained a more effective defence system. The data are corroborated by the weaker structural membrane damage in the drought-exposed tolerant vs. sensitive genotype, according to the MDA test. Hence, diverse chemical types are involved in the non-enzymatic ROS-scavenging system of cotton plants and can be related to the drought tolerance of this important crop. [source] Volume recovery, surface properties and membrane integrity of Lactobacillus delbrueckii subsp. bulgaricus dehydrated in the presence of trehalose or sucroseJOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2007E.E. Tymczyszyn Abstract Aims:, Although the practical importance of adding sugars before drying is well known, the mechanism of protection of bacteria by sugars is not clear. The response of the dehydrated micro-organisms to rehydration is analysed in terms of structural and functional changes, and correlated with their potentiality to grow in rich media. These aspects are related with the membrane integrity and the metabolic state of the rehydrated bacteria, measured by means of surface properties and permeability. To attain this objective, Lactobacillus delbrueckii subsp. bulgaricus was dehydrated in the presence and in the absence of sucrose and trehalose. The bacterial response upon rehydration was investigated by determining: (i) the lag time of the bacterial growing in rich media, (ii) the restoration of the surface properties and the cellular volume and (iii) the membrane integrity. Methods and Results:,Lactobacillus delbrueckii subsp. bulgaricus was grown in MRS at 37°C overnight [De Man et al. (1960)J Appl Bacteriol 23, 130] and then dehydrated for 10, 20 and 30 min at 70°C in a vacuum centrifuge. The lag time of micro-organisms was determined by optical density changes after rehydration. The surface properties were determined by measuring the zeta potential of the bacteria suspended in aqueous solution. The cellular volume recovery was measured, after stabilization in saline solution, by light scattering and by the haematocrit method [Alemohammad and Knowles (1974)J Gen Microbiol 82, 125]. Finally, the membrane integrity has been determined by using specific fluorescent probes [SYTO 9 and propidium iodide, (PI)] that bind differentially depending on the integrity of the bacterial membrane. The lag time of Lact. delbrueckii subsp bulgaricus, dehydrated by heat in the presence of sucrose or trehalose and after that rehydrated, was significantly shortened, when compared with that obtained for bacteria dried in the absence of sugars. In these conditions, trehalose and sucrose maintained the zeta potential and the cell volume close to the control (nondried) cells. However, the membrane integrity, measured with fluorescent probes, was maintained only when cells were dehydrated for 10 min in the presence of sugars. For larger times of dehydration, the membrane integrity was not preserved, even in the presence of sugars. Conclusions:, When the micro-organisms are dehydrated in the absence of protectants, the membrane damage occurs with a decrease in the absolute value of the zeta potential and a decrease in the cellular volume recovered after rehydration. In contrast, when the zeta potential and the cellular volume are restored after rehydration to that corresponding to nondried cells, the micro-organisms are able to recover and grow with a reduced lag time. This can only be achieved when the dehydration is carried out in the presence of sugars. At short dehydration times, the response is associated with the preservation of the membrane integrity. However, for longer times of dehydration the zeta potential and volume recovery occurs in the presence of sugars in spite of a severe damage at membrane level. In this condition, cells are also recovered. In conclusion, to predict the ability of growing after dehydration, other bacterial structural parameters besides membrane integrity, such as zeta potential and cellular volume, should be taken into account. Significance and Impact of the Study:, The correlation of the lag time with the surface and permeability properties is of practical importance because the correlation of these two parameters with cell viability, allow to determine the potential bacterial capacity to grow in a rich medium after the preservation procedure, without necessity of performing a kinetic curve of growth, which is certainly time-consuming. [source] Methyl tert -butyl ether (MTBE)-induced cytotoxicity and oxidative stress in isolated rat spermatogenic cellsJOURNAL OF APPLIED TOXICOLOGY, Issue 1 2007Dongmei Li Abstract Methyl tert -butyl ether (MTBE) is a class of synthetic organic chemical. In the USA, MTBE pollution is regarded as a serious environmental problem. The objective of the present study was to investigate the cytotoxic effects and oxidative stress induced by MTBE in isolated rat spermatogenic cells. In cytotoxic experiments, spermatogenic cells isolated from the testes of adult Sprague-Dawley rats by a mechanical procedure without the use of trypsin were incubated with medium alone (control), 0.5, 5, 50 mm MTBE, respectively, for 6, 12 and 18 h. MTT assay, staining with fluorescein diacetate (FDA) and propidium iodide (PI) and flow cytometric analyses were used. In oxidative stress experiments, the spermatogenic cells were incubated with medium alone (control) and with 0.5, 50 ,m, 5 mm MTBE. For 1, 2, 6, 12, 18 h incubation, ROS production was tested using a 2,,7,-dichlorofluorescein diacetate (DCHF-DA) probe; for 1, 3, 6, 12, 18 h incubation, cytosolic superoxide dismutase (SOD) and extracellular SOD (SODEX) activity was assessed; and for 18 h incubation, lipid peroxidation was assessed. The results showed that MTBE at high doses significantly decreased the spermatogenic cell viability and increased plasma membrane damage and the ratio of necrotic cells compared with the control. Assessment of the MTBE-induced oxidative stress revealed that MTBE increased the production of reactive oxygen species (ROS) and enhanced lipid peroxidation. In addition, although SODEX activity increased at a high dose level, cytosolic SOD activity decreased. These results suggest that an increase of MTBE-induced ROS production and an enhancement of membrane lipid peroxidation may play an important role in its cytotoxicity in isolated rat spermatogenic cells. Copyright © 2006 John Wiley & Sons, Ltd. [source] Metabolic syndrome and mitochondrial function: Molecular replacement and antioxidant supplements to prevent membrane peroxidation and restore mitochondrial function,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2007Garth L. Nicolson Abstract Metabolic syndrome consists of a cluster of metabolic conditions, such as hypertriglyeridemia, hyper-low-density lipoproteins, hypo-high-density lipoproteins, insulin resistance, abnormal glucose tolerance and hypertension, that,in combination with genetic susceptibility and abdominal obesity,are risk factors for type 2 diabetes, vascular inflammation, atherosclerosis, and renal, liver and heart disease. One of the defects in metabolic syndrome and its associated diseases is excess cellular oxidative stress (mediated by reactive oxygen and nitrogen species, ROS/RNS) and oxidative damage to mitochondrial components, resulting in reduced efficiency of the electron transport chain. Recent evidence indicates that reduced mitochondrial function caused by ROS/RNS membrane oxidation is related to fatigue, a common complaint of MS patients. Lipid replacement therapy (LRT) administered as a nutritional supplement with antioxidants can prevent excess oxidative membrane damage, restore mitochondrial and other cellular membrane functions and reduce fatigue. Recent clinical trials have shown the benefit of LRT plus antioxidants in restoring mitochondrial electron transport function and reducing moderate to severe chronic fatigue. Thus LRT plus antioxidant supplements should be considered for metabolic syndrome patients who suffer to various degrees from fatigue. J. Cell. Biochem. 100: 1352,1369, 2007. © 2007 Wiley-Liss, Inc. [source] EFFECT OF COMBINED UNDERWATER PROCESSING AND MILD PRECUT HEAT TREATMENT ON THE SENSORY QUALITY AND STORAGE OF FRESH-CUT CANTALOUPE MELONJOURNAL OF FOOD QUALITY, Issue 4 2010KAREN L. BETT-GARBER ABSTRACT Improvement of storage quality of fresh-cut cantaloupe using a combination precut heat treatment and a modified underwater cutting treatment was determined. Eating quality was evaluated using descriptive sensory analysis, and fruit integrity was measured with respiration, cell leakage and product weight loss. Treatments included (1) control (no treatment); (2) making the first longitudinal cut underwater; (3) mild precut heat treatment in a water bath at 60C for 60 min; and (4) combination of precut heat treatment and the underwater cutting methods. Precut heating and processing underwater resulted in more intense fruity/melon flavor compared to conventional processed fresh-cut fruit. Reduced electrolyte leakage and enhanced membrane integrity were observed in all three experimental treatments, as evidenced by lower conductivity measurements. The underwater cut and combined treatments significantly reduced respiration during fresh-cut storage, reflecting less physical stress and membrane damage. Weight loss was not significantly affected by any treatment during fresh-cut storage. PRACTICAL APPLICATIONS There is a steady increase in the consumption of fresh-cut produce. To enhance the storage quality of fresh-cut cantaloupe melon, two minimal processing techniques were examined separately and combined. The methods are mild heat treatment of the whole melon at 60C for 60 min then cooling to 4C for 24 h, cutting the cantaloupe in half and removing the seeds while submerged in a calcium chloride and water solution, and the combination of the two treatments. These methods are simple and can be utilized by small or large processors to maintain sensory quality and fruit integrity during storage. [source] Differential Responses of the Activities of Antioxidant Enzymes to Thermal Stresses between Two Invasive Eupatorium Species in ChinaJOURNAL OF INTEGRATIVE PLANT BIOLOGY, Issue 4 2008Ping Lu Abstract The effect of thermal stress on the antioxidant system was investigated in two invasive plants, Eupatorium adenophorum Spreng. and E. odoratum L. The former is sensitive to high temperature, whereas the latter is sensitive to low temperature. Our aim was to explore the relationship between the response of antioxidant enzymes and temperature in the two invasive weeds with different distribution patterns in China. Plants were transferred from glasshouse to growth chambers at a constant 25 °C for 1 week to acclimatize to the environment. For the heat treatments, temperature was increased stepwise to 30, 35, 38 and finally to 42 °C. For the cold treatments, temperature was decreased stepwise to 20, 15, 10 and finally to 5 °C. Plants were kept in the growth chambers for 24 h at each temperature step. In E. adenophorum, the coordinated increase of the activities of antioxidant enzymes was effective in protecting the plant from the accumulation of active oxygen species (AOS) at low temperature, but the activities of catalase (CAT), guaiacol peroxidase (POD), ascorbate peroxidase (APX), glutathione reductase (GR), and monodehydroascorbate reductase (MDAR) were not accompanied by the increase of superoxide dismutase (SOD) during the heat treatments. As a result, the level of lipid peroxidation in E. adenophorum was higher under heat stress than under cold stress. In E. odoratum, however, the lesser degree of membrane damage, as indicated by low monodehydroascorbate content, and the coordinated increase of the oxygen. Detoxifying enzymes were observed in heat-treated plants, but the antioxidant enzymes were unable to operate in cold stress. This indicates that the plants have a higher capacity for scavenging oxygen radicals in heat stress than in cold stress. The different responses of antioxidant enzymes may be one of the possible mechanisms of the differences in temperature sensitivities of the two plant species. [source] Cytotoxicity evaluation of enzyme inhibitors and absorption enhancers in Caco-2 cells for oral delivery of salmon calcitoninJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2004Rakhi B. Shah Abstract The usefulness of enzyme inhibitors and absorption enhancers with least mucosal cell cytotoxicity was evaluated on Caco-2 cell monolayers. The temporal cytotoxicity of several protease inhibitors at 500 ,g/mL (e.g., turkey and chicken ovomucoids, aprotinin, and Protease Inhibitor Cocktail) and absorption enhancers [e.g., cholate (3%), glycocholate (3%), glycosursodeoxycholate (3%), ethylenediaminetetraacetic acid (EDTA, 0.1%), hydroxypropyl-,-cyclodextrin (HP-,-CD, 5%), hydroxypropyl-,-cylcodextrin (HP-,-CD, 5%), ,-cylcodextrin (,-CD, 5%), tetradecyl-,- D -maltoside (0.25%), octylglucoside (0.25%), citric acid (10%), glycyrrhetinic acid (0.34 mM), and Tween-80® (0.1%)] was measured by monitoring their effect on Caco-2 cell viability. Cell viability was measured by mannitol permeability measurements, transepithelial electrical resistance (TEER) measurements, DNA-propidium iodide staining assay, and WST-1 assay (tetrazolium salt based assay). Sodium dodecyl sulfate (0.1%), a potent surfactant, was used as a positive control. Chicken and turkey ovomucoids were nontoxic to cells as evaluated by all the methods used. Aprotinin decreased the TEER, whereas plasma membrane damage was seen with Protease Inhibitor Cocktail after a 24-h period. With respect to the absorption enhancers, the toxicity increased directly as a result of an increase in the time of incubation. The enhancers EDTA and HP-,-CD can be used safely for a short period of time, whereas glycosursodeoxycholate, glycyrrhetinic acid, octylglucoside, HP-,-CD, and ,-CD can be used for a longer period. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93: 1070,1082, 2004 [source] The role of surfactants in the reversal of active transport mediated by multidrug resistance proteinsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2003Katrijn Bogman Abstract A variety of seven nonionic, one amphoteric and, one anionic surfactant that are applied or investigated as surfactants in drug formulation, were analyzed for their capacity to modulate carrier-mediated transport by efflux pumps. Two cell lines, murine monocytic leukemia cells overexpressing P-glycoprotein (P-gp) and Madin-Darby canine kidney cells stably overexpresssing human multidrug resistance-associated protein 2 (MRP2), were used as test systems. The modulation of P-gp and of MRP2 function was studied by the reversal of rhodamine 123 and of methylfluorescein-glutathione conjugate transport, respectively. Mechanisms that were not transporter related and could lead to misinterpretations were identified, such as probe quenching, probe encapsulation by micelles, and membrane damage. P-gp-mediated rhodamine 123 transport was inhibited by five nonionic surfactants in a concentration-dependent manner and in the order TPGS,>,Pluronic PE8100,>,Cremophor EL,>,Pluronic PE6100,,,Tween 80. In contrast, none of the surfactants showed a significant inhibition of MRP2-mediated efflux in Madin-Darby canine kidney/MRP2 cells. In conclusion, the results indicate that surfactants demonstrate a transporter-specific interaction, rather than unspecific membrane permeabilization. The present analysis offers insight in the possible mechanisms of surfactant interactions with biological membranes and could help to identify specific drug formulations. © 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:1250,1261, 2003 [source] Beer But Not Wine, Hard Liquors, or Pure Ethanol Stimulates Amylase Secretion of Rat Pancreatic Acinar Cells In VitroALCOHOLISM, Issue 9 2009Andreas Gerloff Background:, In contrast to pure ethanol, the effect of alcoholic beverages on the exocrine pancreas is greatly unknown. Besides ethanol, alcoholic beverages contain numerous nonalcoholic constituents which might have pathophysiological effects on the pancreas. The aim of the present study was to investigate whether some commonly used alcoholic beverages and pure ethanol influence the main function of rat pancreatic acinar cells, i.e., enzyme output in vitro. Methods:, Rat pancreatic AR4-2J cells were differentiated by dexamethasone treatment for 72 hours and freshly isolated pancreatic acini were prepared from Sprague,Dawley rats using collagenase digestion. After incubation of cells in the absence or presence of 1 to 10% (v/v) beer (containing 4.7% v/v ethanol), 10% (v/v) wine (containing 10.5 to 12.5% v/v ethanol), 10% (v/v) hard liquor (such as whisky, rum, and gin), or of the corresponding ethanol concentrations (4.03 to 80.6 mM) for 60 minutes, protein secretion was measured using amylase activity assay. Results:, Incubation of AR4-2J cells with beer caused a dose-dependent stimulation of basal amylase secretion that was significant at doses of beer above 0.5% (v/v). Stimulation with 10% (v/v) beer induced 92.7 ± 25.2% of maximal amylase release in response to the most effective cholecystokinin (CCK) concentration (100 nM). In contrast, ethanol (up to 80.6 mM) did neither stimulate nor inhibit basal amylase release. Lactate dehydrogenase measurement after treatment of AR4-2J cells with beer for 24 hours indicated that the increase of amylase release was not due to cell membrane damage. Wine and hard liquor had no effect on basal amylase secretion neither diluted to the ethanol concentration of beer nor undiluted. In freshly isolated rat pancreatic acinar cells beer dose-dependently stimulated amylase secretion in a similar manner as in AR4-2J cells. Conclusions:, Our data demonstrate that beer dose-dependently increases amylase output. Since neither ethanol nor the other alcoholic beverages tested caused stimulation of amylase release, our findings indicate that nonalcoholic constituents specific for beer are responsible for this increase. These as yet unknown compounds have to be identified and considered in further studies of ethanol-induced pathological and functional changes of the pancreas. [source] Borrelia burgdorferi membranes are the primary targets of reactive oxygen speciesMOLECULAR MICROBIOLOGY, Issue 3 2008Julie A. Boylan Summary Spirochetes living in an oxygen-rich environment or when challenged by host immune cells are exposed to reactive oxygen species (ROS). These species can harm/destroy cysteinyl residues, iron-sulphur clusters, DNA and polyunsaturated lipids, leading to inhibition of growth or cell death. Because Borrelia burgdorferi contains no intracellular iron, DNA is most likely not a major target for ROS via Fenton reaction. In support of this, growth of B. burgdorferi in the presence of 5 mM H2O2 had no effect on the DNA mutation rate (spontaneous coumermycin A1 resistance), and cells treated with 10 mM t -butyl hydroperoxide or 10 mM H2O2 show no increase in DNA damage. Unlike most bacteria, B. burgdorferi incorporates ROS-susceptible polyunsaturated fatty acids from the environment into their membranes. Analysis of lipoxidase-treated B. burgdorferi cells by Electron Microscopy showed significant irregularities indicative of membrane damage. Fatty acid analysis of cells treated with lipoxidase indicated that host-derived linoleic acid had been dramatically reduced (50-fold) in these cells, with a corresponding increase in the levels of malondialdehyde by-product (fourfold). These data suggest that B. burgdorferi membrane lipids are targets for attack by ROS encountered in the various stages of the infective cycle. [source] Roles of antioxidants on prolonged storage of avian spermatozoa in vivo and in vitroMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 3 2003Christelle Bréque Abstract This review focuses on natural and assisted prevention against lipid peroxidation in avian spermatozoa. The presence of high levels of n-6 polyunsaturated fatty acids (PUFAs) in the plasma membrane creates favorable conditions for the formation of peroxidative products, a major cause of membrane damage which may ultimately impair male fertility. However, a complex antioxidant system involving vitamin C, vitamin E and GSH is naturally present in avian semen. Coupled with a battery of enzymatic defenses (e.g., SOD, GSH-Px either Se- or non-Se-dependent), this system acts to prevent or restrict the formation and propagation of peroxides. The presence of specialized sites dedicated to prolonged sperm storage in avian females raises the question of durable protection of sperm membranes against peroxidation. Preliminary observations have revealed the presence of a specific antioxidant system at these sites in which vitamin C could exert a major role. From a practical standpoint, the extensive use of artificial insemination in poultry, along with the emergence in some species of workable techniques to cryopreserve spermatozoa, demand better control of peroxidation occurring in the plasma membrane of spermatozoa before or during storage. Dietary supplementation with vitamin E is effective in limiting lipid peroxidation of sperm plasma membranes, both in chickens and turkeys. In addition, organic Se with or without vitamin E stimulates Se-GSH-Px activity in seminal plasma. Preliminary observations in female chickens have also revealed the effectiveness of dietary supplementation with vitamin E, organic selenium or both to sustain fertility in aging flocks. Mol. Reprod. Dev. 66: 314,323, 2003. © 2003 Wiley-Liss, Inc. [source] Detection and Prevention of Ocular Phototoxicity of Ciprofloxacin and Other Fluoroquinolone Antibiotics,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2010Baozhong Zhao Fluoroquinolone (FLQ) drugs are a potent family of antibiotics used to treat infections including ocular infections. To determine if these antibiotics may be phototoxic to the eye, we exposed human lens epithelial cells to 0.125,1 mm FLQs (ciprofloxacin [Cipro], lomefloxacin [Lome], norfloxacin [Nor] and ofloxacin [Ofl]), the precursor quinolone nalidixic acid (Nalid) and UVA radiation (2.5 J cm,2). Based on fluorescence confocal microscopy, FLQs are diffused throughout the cytoplasm and preferentially located in the lysosomes of lens epithelial cells. Neither FLQ exposure alone nor UVA exposure alone reduced cell viability. However, with exposure to UVA radiation the FLQs studied (Cipro, Nor, Lome and Ofl) induced a phototoxic reaction that included necrosis, apoptosis, loss of cell viability as measured by MTS, and membrane damage as determined by the lactate dehydrogenase assay. Both Nalid and all FLQs studied (Cipro, Nor, Lome and Ofl) photopolymerized the lens protein ,-crystallin. Phototoxic damage to lens epithelial cells and/or ,-crystallin will lead to a loss of transparency of the human lens. However, if precautions are taken to filter all UV radiation from the eye while taking these antibiotics, eye damage may be prevented. [source] Ultraviolet B Light-induced Nitric Oxide/Peroxynitrite Imbalance in Keratinocytes,Implications for Apoptosis and NecrosisPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2010Shiyong Wu Elevation of nitric oxide (NO,) can either promote or inhibit ultraviolet B light (UVB)-induced apoptosis. In this study, we determined real-time concentration of NO, and peroxynitrite (ONOO,) and their role in regulation of membrane integrity and apoptosis. Nanosensors (diameter 300,500 nm) were used for direct in situ simultaneous measurements of NO, and ONOO, generated by UVB in cultured keratinocytes and mice epidermis. An exposure of keratinocytes to UVB immediately generated ONOO, at maximal concentration of 190 nm followed by NO, release with a maximal concentration of 91 nm. The kinetics of UVB-induced NO,/ONOO, was in contrast to cNOS agonist stimulated NO,/ONOO, from keratinocytes. After stimulating cNOS by calcium ionophore (CaI), NO, release from keratinocytes was followed by ONOO, production. The [NO,] to [ONOO,] ratio generated by UVB decreased below 0.5 indicating a serious imbalance between cytoprotective NO, and cytotoxic ONOO,,a main component of nitroxidative stress. The NO,/ONOO, imbalance increased membrane damage and cell apoptosis was partially reversed in the presence of free radical scavenger. The results suggest that UVB-induced and cNOS-produced NO, is rapidly scavenged by photolytically and enzymatically generated superoxide (O2,,) to produce high levels of ONOO,, which enhances oxidative injury and apoptosis of the irradiated cells. [source] 5-Aminolevulinic Acid-Based Photodynamic Therapy in Leukemia Cell HL60,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2004Su-Juan Zhang ABSTRACT A study to explore the optimal experimental parameters and the photosensitization of 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) in promyelocytic leukemia cell HL60 has been conducted, in which HL60 cells and their control groups, peripheral blood mononuclear cell (PBMC), first are incubated with different concentrations of ALA in dark for different periods of time and then followed by irradiating with different wavebands for different fluences. Fluorescence microscope and spectrofluorometer have been used to detect the fluorescence of protoporphyrin IX (PpIX) endogenously produced by ALA. The response of the cells to ALA-PDT was evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2-5-diphenyl-2H-tetrazolium bromide (MTT) assay (interval between irradiation and the MTT assay is 24 h) and by flow cytometry (the length of time between irradiation and the flow assay is 30 min). MTT results will reflect the relative number of metabolically active mitochondria in the population. Propidium iodide uptake in flow cytometry will test for membrane damage. The results of parameter experiments were obtained: 1 × 105/mL HL60 cell was first incubated with 1 mmol/L ALA in dark for 4 h and the maximum fluorescence of PpIX level appeared; then irradiated with 410 nm (4 mW/cm2) for 14.4 J/cm2 and maximum photodamage to membrane and mitochondrial function of HL60 cell resulted. With the normal granulocytes, such response was not detected. Therefore a hypothetical idea can be brought forward that ALA-based PDT can be used for inactivation of leukemia cell HL60 and these optimal parameters may be useful for clinical application. [source] The effect of drought and ultraviolet radiation on growth and stress markers in pea and wheatPLANT CELL & ENVIRONMENT, Issue 12 2001V. Alexieva Abstract It emerged recently that there is an inter-relationship between drought and ultraviolet-B (UV-B) radiation in plant responses, in that both stresses provoke an oxidative burst. The purpose of this investigation was to compare the effects and interaction of drought and UV-B in wheat and pea. The absence of changes in relative leaf water content (RWC) after UV-B treatments indicate that changes in water content were not involved. RWC was the main factor resulting in reduced growth in response to drought. Increases in anthocyanin and phenols were detected after exposure to UV-B. The increases do not appear to be of sufficient magnitude to act as a UV-B screen. UV-B application caused greater membrane damage than drought stress, as assessed by lipid peroxidation as well as osmolyte leakage. An increase in the specific activities of antioxidant enzymes was measured after UV-B alone as well as after application to droughted plants. Proline increased primarily in drought-stressed pea or wheat. Proline may be the drought-induced factor which has a protective role in response to UV-B. The physiological and biochemical parameters measured indicate the UV-B light has stronger stress effectors than drought on the growth of seedlings of both species. The two environmental stresses acted synergistically to induce protective mechanisms in that pre-application of either stress reduced the damage caused by subsequent application of the other stress. [source] A role of Toc33 in the protochlorophyllide-dependent plastid import pathway of NADPH:protochlorophyllide oxidoreductase (POR) A,THE PLANT JOURNAL, Issue 1 2005Steffen Reinbothe Summary NADPH:protochlorophyllide oxidoreductase (POR) A is a key enzyme of chlorophyll biosynthesis in angiosperms. It is nucleus-encoded, synthesized as a larger precursor in the cytosol and imported into the plastids in a substrate-dependent manner. Plastid envelope membrane proteins, called protochlorophyllide-dependent translocon proteins, Ptcs, have been identified that interact with pPORA during import. Among them are a 16-kDa ortholog of the previously characterized outer envelope protein Oep16 (named Ptc16) and a 33-kDa protein (Ptc33) related to the GTP-binding proteins Toc33 and Toc34 of Arabidopsis. In the present work, we studied the interactions and roles of Ptc16 and Ptc33 during pPORA import. Radiolabeled Ptc16/Oep16 was synthesized from a corresponding cDNA and imported into isolated Arabidopsis plastids. Crosslinking experiments revealed that import of 35S-Oep16/Ptc16 is stimulated by GTP. 35S-Oep16/Ptc16 forms larger complexes with Toc33 but not Toc34. Plastids of the ppi1 mutant of Arabidopsis lacking Toc33, were unable to import pPORA in darkness but imported the small subunit precursor of ribulose-1,5-bisphosphate carboxylase/oxygenase (pSSU), precursor ferredoxin (pFd) as well as pPORB which is a close relative of pPORA. In white light, partial suppressions of pSSU, pFd and pPORB import were observed. Our results unveil a hitherto unrecognized role of Toc33 in pPORA import and suggest photooxidative membrane damage, induced by excess Pchlide accumulating in ppi1 chloroplasts because of the lack of pPORA import, to be the cause of the general drop of protein import. [source] Health monitoring of plants by their emitted volatiles: trichome damage and cell membrane damage are detectable at greenhouse scaleANNALS OF APPLIED BIOLOGY, Issue 3 2009R.M.C. Jansen Abstract Pathogen attack and herbivore infestation have a major impact on plant health. In a model study, these two plant health issues were simulated to study whether plant health can be monitored at greenhouse scale through the analysis of volatile organic compounds (VOCs) in greenhouse atmosphere. To simulate pathogen attack and herbivore infestation, we repeatedly stroked the stems of tomato plants (Lycopersicon esculentum) and repeatedly removed their side shoots. In addition, we studied the effect of fruit picking on the concentration of plant-emitted VOCs in greenhouse atmosphere. Analysis of air samples obtained before these treatments revealed up to 17 VOCs that are known to be released from tomato plants, of which the most dominant one was the monoterpene ,-phellandrene. When plants were 7 weeks old, the concentration of this VOC was approximately 0.06 ppbv before treatment. When plants were 12 weeks old, this concentration was raised to approximately 0.14 ppbv. Stroking of the stems, removing the side shoots and fruit picking resulted in an increase in the concentrations of all mono- and most sesquiterpenes up to 60-fold, which was expected because these VOCs are well-known constituents of trichomes. The treatments did not result in substantially increased concentrations of the stress-related compounds ,-copaene, methyl salicylate and (E,E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene. In contrast to stroking and fruit picking, shoot removal resulted in the emission of the lipoxygenase-derived product (Z)-3-hexenol in greenhouse atmosphere expressing cell membrane degradation. The findings presented in this paper focus on the feasibility of monitoring plant health through the analysis of VOCs in greenhouse air, but findings might also be relevant for atmospheric chemistry. [source] Toxic Effects of Lipid-Mediated Gene Transfer in Ventral Mesencephalic Explant CulturesBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2006Matthias Bauer We introduce a protocol to monitor toxic effects of two non-viral lipid-based gene delivery protocols using CNS primary tissue. Cell membrane damage was monitored by quantifying cellular uptake of propidium iodide and release of cytosolic lactate dehydrogenase to the culture medium. Using a liposomal transfection reagent, cell membrane damage was already seen 24 hr after transfection. Nestin-positive target cells, which were used as morphological correlate, were severely diminished in some areas of the cultures after liposomal transfection. In contrast, the non-liposomal transfection reagent revealed no signs of toxicity. This approach provides easily accessible information of transfection-associated toxicity and appears suitable for prescreening of transfection reagents. [source] A novel purification strategy for retrovirus gene therapy vectors using heparin affinity chromatographyBIOTECHNOLOGY & BIOENGINEERING, Issue 4 2005María de las Mercedes Segura Abstract Membrane separation and chromatographic technologies are regarded as an attractive alternative to conventional academic small-scale ultracentrifugation procedures used for retrovirus purification. However, despite the increasing demands for purified retroviral vector preparations, new chromatography adsorbents with high specificity for the virus have not been reported. Heparin affinity chromatography is presented here as a novel convenient tool for retrovirus purification. The ability of bioactive retroviral particles to specifically bind to heparin ligands immobilized on a chromatographic gel is shown. A purification factor of 63 with a recovery of 61% of functional retroparticles was achieved using this single step. Tentacle heparin affinity supports captured retroviral particles more efficiently than conventional heparin affinity chromatography supports with which a lower recovery was obtained (18%). Intact, infective retroviral particles were recovered by elution with low salt concentrations (350 mM NaCl). Mild conditions for retrovirus elution from chromatographic columns are required to preserve virus infectivity. VSV-G pseudotyped retroviruses have shown to be very sensitive to high ionic strength, losing 50% of their activity and showing membrane damage after a short exposure to 1M NaCl. We also report a complete scaleable downstream processing scheme for the purification of MoMLV-derived vectors that involves sequential microfiltration and ultra/diafiltration steps for virus clarification and concentration respectively, followed by fractionation by heparin affinity chromatography and final polishing by size-exclusion chromatography. Overall, by using this strategy, a 38% yield of infective particles can be achieved with a final purification factor of 2,000. © 2005 Wiley Periodicals, Inc. [source] Evaluation of Process-Induced Dimensional Changes in the Membrane Structure of Biological Cells Using Impedance MeasurementBIOTECHNOLOGY PROGRESS, Issue 3 2002Alexander Angersbach The impact of high intensity electric field pulses, high hydrostatic pressure, and freezing-thawing on local structural changes of the membrane was determined for potato, sugar beet tissue, and yeast suspensions. On the basis of the electrophysical model of cell systems in biological tissues and suspensions, a method was derived for determining the extent of local damage of cell membranes. The method was characterized by an accurate and rapid on-line determination of frequency-dependent electrical conductivity properties from which information on microscopic events on cellular level may be deduced. Evaluation was based on the measurement of the relative change in the sampleapos;s impedance at characteristically low ( fl) and high ( fh) frequencies within the ,-dispersion range. For plant and animal cells the characteristic frequencies were fl , 5 kHz and fh > 5 MHz and for yeast cells in the range fl , 50 kHz and fh > 25 MHz. The observed phenomena were complex. The identification of the underlying mechanisms required consideration of the time-dependent nature of the processing effects and stress reactions of the biological systems, which ranged from seconds to several hours. A very low but significantly detectable membrane damage (0.004% of the total area) was found after high hydrostatic pressure treatment of potato tissue at 200 MPa. The membrane rupture in plant tissue cells was higher after freezing and subsequent thawing (0.9% of total area for potato cells and 0.05,0.07% for sugar beet cells determined immediately after thawing), which increased substantially during the next 2 h. [source] Topical 5-aminolaevulinic acid-photodynamic therapy for the treatment of urethral condylomata acuminataBRITISH JOURNAL OF DERMATOLOGY, Issue 4 2004X.L. Wang Summary Background, Electrocoagulation and laser evaporation for urethral condylomata acuminata have high recurrence rates and can be associated with urethral malformations. Objectives, To investigate the effect of photodynamic therapy (PDT) with topical 5-aminolaevulinic acid (ALA) on urethral condylomata acuminata and to examine the histological changes in lesions of condylomata acuminata after ALA-PDT. Methods, Patients with urethral condylomata (n = 164) were given topical ALA followed by intraurethral PDT through a cylindrical fibre. Patients included 11 individuals with 16 penile or vulval condylomatous lesions which were biopsied before or after treatment; the histological changes were then evaluated by light microscopy and electron microscopy. Results, The complete response rate was 95% and the recurrence rate was 5% after 6,24 months of follow-up. Light microscopy revealed keratinocytes in the middle and upper layers of the epidermis showing marked vacuolation and some necrocytosis 1 and 3 h after PDT. Necrosis in all layers of the epidermis was noted 5 h after PDT. Electron microscopy of keratinocytes revealed distinct ultrastructural abnormalities of mitochondria and the endoplasmic reticulum, and membrane damage. Apoptotic bodies were detected 3 h after PDT and a large number of keratinocytes exhibited necrosis 5 h after PDT. Conclusions, Results suggest that, compared with conventional therapies, topical ALA-PDT is a simple, effective, safe and well-tolerated treatment for urethral condylomata acuminata that is associated with a low recurrence rate. The mechanism might be the triggering of both apoptosis and necrosis by ALA-PDT in human papillomavirus-infected keratinocytes. [source] Inhibition of TRPM2 function by PARP inhibitors protects cells from oxidative stress-induced deathBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2004Barbara A Miller TRPM2 is a member of the transient receptor potential (TRP) protein superfamily of calcium-permeable, voltage-independent ion channels expressed in nonexcitable cells. Activation of TRPM2 by oxidative stress results in calcium influx and susceptibility to cell death, whereas inhibition of TRPM2 function enhances cell survival. In the present edition of this journal, Fonfria et al. demonstrate a role for poly(ADP ribose) polymerase (PARP) as a mediator between oxidative stress and TRPM2 activation. They present evidence that inhibition of either PARP or TRPM2 protects cells from plasma membrane damage and cell death. The therapeutic implications of this important observation are discussed. British Journal of Pharmacology (2004) 143, 515,516. doi:10.1038/sj.bjp.0705923 [source] The relationship between cell membrane damage and lipid peroxidation under the condition of hypoxia-reoxygenation: analysis of the mechanism using antioxidants and electron transport inhibitorsCELL BIOCHEMISTRY AND FUNCTION, Issue 6 2009Daisuke Yajima Abstract We consecutively observed lipid peroxidation and cell membrane damage under the condition of hypoxia-reoxygenation (H/R) in cells and analyzed their mechanisms by using electron transport inhibitors and an antioxidant. In H/R experiments, lipid peroxidation and cell membrane damage were observed during the hypoxia phase. In the reoxygenation phase, lipid peroxidation stopped, while cell membrane damage did not. An antioxidant, n-acetylcystein (NAC), and potassium cyanide (KCN) inhibited lipid peroxidation and cell membrane damage, while rotenone did not inhibit either of them. Although antimycin A did not inhibit lipid peroxidation, it inhibited cell membrane damage during the hypoxia phase but not during the reoxygenation phase. These results suggested that lipid peroxidation can affect cell membrane damage as a trigger during the hypoxia phase and the generation of oxidative stress can vary depending on the inhibition locations in the electron transport system. Copyright © 2009 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||||||||