共查询到20条相似文献,搜索用时 62 毫秒
1.
G. Tapia P. Cornejo J. Ferreira V. Fernández 《Redox report : communications in free radical research》2013,18(4):213-218
SummaryThe influence of acetaminophen (APAP) treatment (400 mg/kg) on Kupffer cell function was studied in the isolated perfused liver by colloidal carbon infusion, concomitantly with parameters related to oxidative stress (thiobarbituric acid reactants (TBARS) formation and glutathione (GSH) content) and tissue injury (sinusoidal efflux of lactate dehydrogenase (LDH)). APAP led to increased rates of hepatic TBARS formation, GSH depletion, and higher sinusoidal LDH efflux compared to control values, without changes in the basal rate of O2 consumption. In addition, APAP significantly enhanced the rate of carbon uptake by perfused livers and the associated carbon-induced O2 consumption, with carbon-induced LDH effluxes being increased by 411% over control values or by 124% compared to basal LDH release in APAP-treated rats. APAP-induced changes in liver TBARS formation and GSH levels were attenuated by gadolinium chloride (GdCl3) pretreatment, whereas those in carbon uptake, carbon-induced respiration, and LDH efflux were abolished. GdCl3 pretreatment decreased liver O2 consumption irrespectively of APAP treatment, an effect that seems to be due to depression of mitochondrial respiration. It is concluded that APAP intoxication enhances Kupffer cell function as assessed in the intact liver, which may represent an important source of reactive O2 species and chemical mediators conditioning the increased oxidative stress status and the tissue injury which developed. 相似文献
2.
E. G. Janzen 《Redox report : communications in free radical research》2013,18(3):155-159
AbstractThe influence of aging on the respiratory activity of stimulated Kupffer cells was investigated in the isolated perfused mouse liver in relation to colloidal carbon phagocytosis, and the content of glutathione (GSH) and protein carbonyls as parameters related to oxidative stress. Livers from aged (22 months) mice exhibited significant 35% and 65% decreases in the carbon uptake and in the carbon-induced O2 consumption compared to young (3 months) animals, respectively, with a concomitant 46% diminution in the carbon-induced O2 consumption/carbon uptake ratio. Hepatic GSH depletion was observed in aged mice compared to young animals, whereas protein oxidation was enhanced. It is concluded that aging leads to an impairment in the functional capacity of Kupffer cells reflected by a substantial reduction in their respiratory burst activity, lessened endocytic capacity and enhanced oxidative stress, that may contribute to increased susceptibility of the liver to noxious challenges. 相似文献
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Summary Electrical stimulation of efferent thoracic vagus nerve (TVN) evoked neurogenic inflammation in respiratory tract of atropine-treated
rats by an undefined mechanism. We explored whether efferent TVN stimulation via substance P facilitates neurogenic inflammation
via action of nuclear factor-κB (NF-κB) activation and reactive oxygen species (ROS) production. Our results showed that increased
frequency of TVN stimulation concomitantly increased substance P-enhanced hypotension, and bronchoconstriction (increases
in smooth muscle electromyographic activity and total pulmonary resistance). The enhanced SP release evoked the appearance
of endothelial gap in silver-stained leaky venules, India-ink labeled extravasation, and accumulations of inflammatory cells
in the respiratory tract, contributing to trachea plasma extravasation as well as increases in blood O2− and H2O2 ROS amount. L-732138 (NK1 receptor antagonist), SR-48968 (NK2 receptor antagonist), dimethylthiourea (H2O2 scavenger) or catechins (O2− and H2O2 scavenger) pretreatment reduced efferent TVN stimulation-enhanced hypotension, bronchoconstriction, and plasma extravasation.
Increased frequency of TVN stimulation significantly upregulated the expression of nuclear factor-κB (NF-κB) in nuclear protein
and intercellular adhesion molecule-1 (ICAM-1) in total protein of the lower respiratory tract tissue. The upregulation of
NF-κB and ICAM-1 was attenuated by NK receptor antagonist and antioxidants. In conclusion, TVN efferent stimulation increases
substance P release to trigger NF-κB mediated ICAM-1 expression and O2− and H2O2 ROS production in the respiratory tract. 相似文献
5.
《Journal of Plant Interactions》2013,8(1):402-411
A hydroponics experiment was conducted to test the effects of sodium nitroprusside (SNP, a donor of NO) supplied with different concentrations on copper (Cu) toxicity in ryegrass seedlings (Lolium perenne L.). Excess Cu (200 µM) reduced chlorophyll content, resulting a decrease in photosynthesis. Cu stress induced the production of hydrogen peroxide (H2O2) and superoxide anion (O2? ?), leading to malondialdehyde (MDA) accumulation. Furthermore, activities of antioxidant enzymes in Cu-treated seedlings such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were decreased. In addition, Cu stress inhibited the uptake of K, Mg, Fe, and Zn and increased Ca content in roots. Moreover, in leaves of Cu-stressed seedlings, K, Fe, and Zn contents were decreased and the contents of Ca and Mg were not affected significantly. In Cu-treated seedlings, Cu concentration in roots was higher than in leaves. Addition of 50, 100, 200 µM SNP in Cu-mediated solutions increased chlorophyll content and photosynthesis, improved antioxidant enzyme activities, reduced Cu-induced oxidative damages, kept intracellular ion equilibrium under Cu stress, increased Cu concentration in roots and inhibited Cu accumulation in leaves. In particular, addition of 100 µM SNP had the best effect on promoting growth of ryegrass seedlings under Cu stress. However, the application of 400 µM SNP had no obvious alleviating effect on Cu toxicity in ryegrass seedlings. 相似文献
6.
Jorge Sans Maria Aguilera Paola Faundez Pilar Troncoso Virginia Fernandez Luis A. Videla 《Free radical research》2013,47(6):489-498
Formation of reactive O2 species in biological systems can be accomplished by copper-(II) (Cu2+) catalysis, with the consequent cytotoxic response. We have evaluated the influence of Cu2+ on the respiratory activity of Kupffer cells in the perfused liver after colloidal carbon infusion. Studies were carried out in untreated rats and in animals pretreated with the Kupffer cell inactivator gadolinium chloride (GdCl3) or with the metallothionein (MT) inducing agent zinc sulphate, and results were correlated with changes in liver sinusoidal efflux of lactate dehydrogenase (LDH) as an index of hepatotoxicity. In the concentration range of 0.1–1 μM, Cu2+ did not modify carbon phagocytosis by Kupffer cells, whereas the carbon-induced liver O2 uptake showed a sigmoidal-type kinetics with a half-maximal concentration of 0.23 μM. Carbon-induced O2 uptake occurred concomitantly with an increased LDH efflux, effects that were significantly correlated and abolished by GdCl3 pretreatment or by MT induction. It is hypothesized that Cu2+ increases Kupffer cell-dependent O2 utilization by promotion of the free radical processes related to the respiratory burst of activated liver macrophages, which may contribute to the concomitant development of hepatocellular injury. 相似文献
7.
The objective of this study was to investigate the specific role of nitric oxide (NO) in the early response of hulless barley roots to copper (Cu) stress. We used the fluorescent probe diaminofluorescein-FM diacetate to establish NO localization, and hydrogen peroxide (H2O2)-special labeling and histochemical procedures for the detection of reactive oxygen species (ROS) in the root apex. An early production of NO was observed in Cu-treated root tips of hulless barley, but the detection of NO levels was decreased by supplementation with a NO scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO). Application of sodium nitroprusside (a NO donor) relieved Cu-induced root inhibition, ROS accumulation and oxidative damage, while c-PTIO treatment had a synergistic effect with Cu and further enhanced ROS levels and oxidative stress. In addition, the Cu-dependent increase in activities of superoxide dismutase, peroxidase and ascorbate peroxidase were further enhanced by exogenous NO, but application of c-PTIO decreased the activities of catalase and ascorbate peroxidase in Cu-treated roots. Subsequently, cell death was observed in root tips and was identified as a type of programed cell death (PCD) by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The addition of NO prevented the increase of cell death in root tips, whereas inhibiting NO accumulation further increased the number of cells undergoing PCD. These results revealed that NO production is an early response of hulless barley roots to Cu stress and that NO contributes to Cu tolerance in hulless barley possibly by modulating antioxidant defense, subsequently reducing oxidative stress and PCD in root tips. 相似文献
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The effect of Ca on Cu toxicity in runner bean plants (Phaseolus coccineus L. cv. Piěkny Jaś) grown hydroponically in nutrient solution was studied. The toxic effect of excess Cu on plants depends on their
age and Ca content in the medium. Copper applied in excess to the plants at the early phase of leaf development strongly limits
the uptake of Ca ions from the nutrient solution, particularly their translocation to leaves. Increased Ca content limits
the inhibitory effect of Cu on leaf growth and decreases the content of chloroplast pigments to the level approximate to that
of control. At this growth stage the effect of excess Cu is at least partially connected with limited Ca transport to leaves.
At the intermediate leaf phase Cu-treated plants react slightly to changed Ca content.
At the end of the primary leaf development increased Ca concentration in the medium intensifies senescence processes induced
by excess Cu. The changes are partially connected with intensified water deficit. Increased Ca content in the nutrient solution
limits Cu accumulation in the individual organs of Cu-treated plants. However, Cu accumulation in leaves is not decreased
at a high level of Ca. Copper generally decreases Ca content in the youngest plants, whereas in the oldest ones only in the
case of a low level of Ca in the nutrient solution. 相似文献
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B. Lincoln Ph.D. H. L. Bonkovsky Lo -Chang Ou 《International journal of biometeorology》1987,31(3):201-210
A syndrome of experimental chronic mountain sickness can be produced in the Hilltop strain of Sprague-Dawley rats by chronic hypobaric hypoxic exposure. This syndrome is characterized by polycythemia, plasma hemoglobinemia, pulmonary hypertension and right ventricular hypertrophy with eventual failure and death. It has generally been assumed that these changes are caused by chronic hypoxemia, not by hypobaric exposureper se. We have now confirmed this directly by showing that chronic normobaric hypoxic exposure (10.5% O2) produces similar hematologic and hemodynamic changes. Further, the addition of hypercapnic exposure to the hypoxic exposure blunted or prevented the effects of the hypoxic exposure probably by stimulating respiration, thus increasing the rate of oxygen delivery to the cells. Changes in the rate-controlling enzymes of hepatic heme metabolism, 5-aminolevulinate synthase and heme oxygenase, and in cytochrome(s) P-450, the major hepatic hemoprotein(s), were also measured in hypoxic and hypercapnic rats. Hypoxia decreased 5-aminolevulinate synthase and increased cytochrome(s) P-450, probably by increasing the size of a regulatory heme pool within hepatocytes. These changes were also prevented by the addition of hypercapnic to hypoxic exposure. 相似文献
13.
Dedifferentiated hepatoma cells, in contrast to most other cell types including hepatoma cells, undergo apoptosis when treated
with lipopolysaccharide (LPS) plus the protein synthesis inhibitor cycloheximide (CHx). We recently reported that the dedifferentiated
hepatoma cells also exhibit a strong and prolonged NF-κB induction phenotype upon exposure to LPS, suggesting that NF-κB signaling
may play a pro-survival role, as reported in several other cell systems. To test the role of NF-κB in preventing LPS-mediated
apoptosis, we examined the dedifferentiated cell line M38. Results show that antioxidants strongly inhibited LPS + CHx-mediated
cell death in the M38 cells, yet only modestly inhibited NF-κB induction. In addition, inhibition of NF-κB translocation by
infection of the M38 cells with an adenoviral vector expressing an IκBα super-repressor did not result in LPS-mediated cell
death. These results suggest that unlike TNFα induction, the cell survival pathway activated in response to LPS is independent
of NF-κB translocation in the dedifferentiated cells. Addition of inhibitors of JNK, p38 and ERK pathways also failed to elicit
LPS-mediated apoptosis similar to that observed when protein synthesis is prevented. Thus, cell survival pathways other than
those involving NF-κB inducible gene expression or other well-known pathways appear to be involved in protecting the dedifferentiated
hepatoma variant cells from LPS-mediated apoptosis. Importantly, this pro-apoptotic function of LPS appears to be a function
of loss of hepatic gene expression, as the parental hepatoma cells resist LPS-mediated apoptosis in the presence of protein
synthesis inhibitors. 相似文献
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Marsillach J Ferré N Camps J Rull A Beltran R Joven J 《Molecular and cellular biochemistry》2008,308(1-2):101-109
Chronic liver diseases are accompanied by changes in the biochemical pathways related to the regulation of apoptosis and extra-cellular
matrix deposition. The present study was designed to investigate, using low density arrays, changes in the hepatic gene expression
together with hepatic biochemical and histological alterations in rats that had liver impairment induced by chronic exposure
to CCl4. Further, we examined the possible recovery of genetic and pathological changes following the cessation of the hepatotoxic
injury. Experimental fibrosis was induced in male Wistar rats by CCl4 administration. Animals were subdivided into two groups. One group was given CCl4 and animals were killed at 8 and 12 weeks of treatment. The other group was treated with CCl4 for 6 weeks, the CCl4 was then stopped and, subsequently, subgroups of animals were killed after 1 and 2 weeks of recovery. CCl4 administration over 12 weeks was associated with significant changes in B-cell leukemia/lymphoma 2, procollagen type I α
2, matrix metalloproteinases 3 and 8, tissue inhibitors of metalloproteinases 1, 2, and 3 and the inhibitor of apoptosis 4
gene expressions. Recovery after CCl4 cessation was associated with changes in procollagen type I α 2, matrix metalloproteinase 7, tissue inhibitors of metalloproteinases
1 and 2, inhibitor of apoptosis 4, and survivin gene expressions. This study shows an association between changes in the expression
of several genes regulating hepatic cell apoptosis, the fibrosis process, and the recovery of the hepatic function after removal
of the toxic injury. 相似文献
16.
Rainer Voisard Nicola Huber Regine Baur Milorat Susa Oliver Ickrath Anton Both Wolfgang Koenig Vinzenz Hombach 《BMC molecular biology》2001,2(1):7-7
Background
Activation of nuclear factor-κB (NF-κB) is one of the key events in early atherosclerosis and restenosis. We hypothesized that tumor necrosis factor-α (TNF-α) induced and NF-κB mediated expression of intercellular adhesion molecule-1 (ICAM-1) can be inhibited by antisense RelA p65 and NF-κB1 p50 oligonucleotides (RelA p65 and NF-κB1 p50). 相似文献17.
Mi Hee Lee Dong-Wook Han Suong-Hyu Hyon Jong-Chul Park 《Apoptosis : an international journal on programmed cell death》2011,16(1):75-85
Animal tumor bioassays and in vitro cell culture systems have demonstrated that epigallocatechin-3-O-gallate (EGCG), the predominant catechin in green tea, possesses anti-proliferative and pro-apoptotic effects on various
cancer cells and tumors. In this study, we investigated the effects of EGCG on cell growth, cell cycle progression, and apoptosis
in human fibrosarcoma HT-1080 cells. The involvement of p53, Bcl-2, Bax, caspases, and nuclear factor-κB (NF-κB) was examined
as a mechanism for the anti-cancer activity of EGCG. Time-dependent intracellular trafficking of EGCG was also determined
using fluorescein isothiocyanate (FITC)-conjugated EGCG (FITC-EGCG). Our data show that EGCG treatment caused dose-dependent
cell growth inhibition, cell cycle arrest at the G0/G1 phase, and DNA fragmentation suggesting the induction of apoptosis in HT-1080 cells. Immunoblot analysis revealed that the
expression of p53, caspase-7 and -9 as well as the ratio of Bax/Bcl-2 protein increased significantly with higher EGCG concentrations
and longer incubation times. Moreover, expression of phosphorylated NF-κB/p65 in HT-1080 cells was inhibited by EGCG treatment
in a dose-dependent manner, while that of unphosphorylated NF-κB/p65 remained unaffected. Here we also reveal time-dependent
internalization of FITC-EGCG into the cytosol of HT-1080 cells and its subsequent nuclear translocation. These results suggest
that EGCG may interrupt exogenous signals directed towards genes involved in proliferation and cell cycle progression. Taken
together, our data indicate that HT-1080 apoptosis may be mediated through the induction of p53 and caspases by the pro-oxidant
activity of internalized EGCG, as well as suppression of Bcl-2 and phosphorylated NF-κB by the antioxidant activity of EGCG. 相似文献
18.
Merentie M Uimari A Pietilä M Sinervirta R Keinänen TA Vepsäläinen J Khomutov A Grigorenko N Herzig KH Jänne J Alhonen L 《Amino acids》2007,33(2):323-330
Summary. The markers of oxidative stress and inflammation were studied in acute pancreatitis in transgenic rats exhibiting activated
polyamine catabolism. In addition, the effect of bismethylspermine (Me2Spm) pretreatment, preventing pancreatitis in this model, on these mediators was investigated. Lipid peroxidation was increased
at 6 and 24 h after induction of pancreatitis. These changes as well as the markedly decreased superoxide dismutase activity
at 24 h were abolished by Me2Spm pretreatment. Glutathione level and catalase activity changed transiently, and the effect of Me2Spm was clear at 24 h. Serum inflammatory cytokine levels increased already at 4 h whereas NF-κB was distinctly activated
only at 24 h. Me2Spm prevented the increase in TNF-α and IL-6 while it had no effect on NF-κB activation. These results show that typical inflammatory
and, to a lesser degree, some oxidative stress mediators are involved and beneficially affected by the disease-ameliorating
polyamine analogue in our pancreatitis model. 相似文献
19.
Hongmei Liu Congcong Zhang Kaixun Huang 《Journal of biological inorganic chemistry》2011,16(5):671-681
Experimental studies have demonstrated that oral administration of lanthanum chloride (LaCl3) inhibits the development of atherosclerosis, but the related mechanism has not been fully elucidated. Oxysterols are toxic
to the vascular endothelial cells which are important in preventing the formation and progression of atheromatous plaque.
In this study, we examined the effect of LaCl3 on oxysterol cholestane-3β,5α,6β-triol (Triol)-induced apoptosis and the related mechanisms in ECV-304 cells, a presumptive
endothelial cell line. Incubation with Triol resulted in apoptosis of ECV-304 cells, as determined by Hoechst 33342 staining,
fluorescein isothiocyanate labeled annexin V/propidium iodide double staining, and the loss of mitochondrial membrane potential.
Triol activated extracellular-signal-regulated kinase (ERK) and nuclear factor κB (NF-κB), and inhibition of Triol-activated
ERK and NF-κB signaling by specific inhibitors attenuated apoptosis induction by Triol in ECV-304 cells. Pretreatment with
LaCl3 (1 μM) for 12 h before exposure to Triol decreased Triol-mediated apoptosis as well as activation of ERK and NF-κB. In addition,
Triol induced oxidative stress in ECV-304 cells, manifested by the increase of intracellular reactive oxygen species generation
and malondialdehyde level, and the reduction of the content of total protein thiols and the activity of antioxidant glutathione
peroxidases; LaCl3 pretreatment significantly reversed these effects. Finally, LaCl3 pretreatment significantly inhibited the increases of intracellular Ca2+ concentration induced by Triol. Our study suggests that Triol induced ECV-304 cell apoptosis, and LaCl3 could suppress this effect probably by inhibiting intracellular Ca2+ concentration elevation, oxidative stress, as well as activation of ERK and NF-κB signaling pathways. 相似文献
20.
《Peptides》2013
Diabetic peripheral neuropathy is one the most common complications of diabetes mellitus and frequently results in clinically significant morbidities such as pain, foot ulcers and amputations. The diabetic condition progresses from early functional changes to late, poorly reversible structural changes. The chronic hyperglycemia measured alongside diabetes development is associated with significant damage and failure of various organs. In the present study diabetes was induced in male Wistar rats by a single dose of streptozotocin (STZ) and the association between the BKB1-R and the oxidative stress and Na+-K+ ATPase activity in nervous tissues was analysed. The results showed that the resulting hyperglycemia induced a reduction of the neuronal electrical function integrity and increased oxidative stress in the sciatic nerve homogenates of 30 days diabetic rats. Malondialdehyde (MDA) used as a marker of oxidative stress was elevated whereas Biological Antioxidant Potential (BAP), glutathion (GSH) levels and superoxide dismutase (SOD) activity were decreased. Treatment of the rats 3 days before the end of the 4 week period with the BKB1 antagonist R-954 restored the neuronal activity and significantly attenuated the oxidative stress as shown by the level of the various markers returning close to levels found in control rats. Our results suggest that the BKB1-R subtype is overexpressed in sciatic nerve during the STZ-induced diabetes development as evidenced by inhibitory effects of the BKB1-R antagonist R-954. The beneficial role of BKB1-R antagonist R-954 for the treatment of diabetic neuropathy is also suggested. 相似文献