Lipoxin A4 methyl ester protects PC12 cells from ketamine-induced neurotoxicity via the miR-22/BAG5 pathway

2021 ◽  
pp. 096032712110516
Author(s):  
Xue-song Wang ◽  
Long-cheng Li ◽  
Xue Zhang ◽  
Jin Gao
Keyword(s):  
Methyl Ester ◽  
Pc12 Cells ◽  
In Vitro Assays ◽  
Protective Mechanism ◽  
Dependent Manner ◽  
Protective Effects ◽  
Concentration Dependent Manner ◽  
Pheochromocytoma Pc12 ◽  
High Doses

Objective Ketamine is an anesthetic that induces neurotoxicity when administered at high doses. In this work, we explored the protective effects of lipoxin A4 methyl ester (LXA4 ME) against ketamine-induced neurotoxicity and the underlying protective mechanism in pheochromocytoma (PC12) cells. Methods PC12 cells were treated with 50 μM of ketamine and different LXA4 ME concentrations of LXA4 ME (5–50 nM) for 24 h, and their viability, apoptosis, and oxidative status were assessed. Results Quantitative real-time polymerase chain reaction experiments showed that ketamine downregulated miR-22 expression and upregulated Bcl-2-associated athanogene 5 (BAG5) in PC12 cells in a concentration-dependent manner. LXA4 ME induced the opposite effects, thus attenuating ketamine-induced neurotoxicity. Further in vitro assays showed that miR-22 directly targeted BAG5, thus promoting cell viability by suppressing cell apoptosis and oxidative stress. Under expression miR-22 or upregulation of BAG5 antagonized the effects of LXA4 ME. Conclusion LXA4 ME can protect PC12 cells from ketamine-induced neurotoxicity by activating the miR-22/BAG5 signaling pathway. Thus, LXA4 ME can be used as a protective drug against ketamine-induced neural damage.

Properties of neuroprotective cell-permeant Ca2+ chelators: effects on [Ca2+]i and glutamate neurotoxicity in vitro

1994 ◽  
Vol 72 (4) ◽  
pp. 1973-1992 ◽  
Author(s):  
M. Tymianski ◽  
M. P. Charlton ◽  
P. L. Carlen ◽  
C. H. Tator
Keyword(s):  
Time Course ◽  
Dependent Manner ◽  
Protective Effects ◽  
Tetraacetic Acid ◽  
Acetoxymethyl Ester ◽  
Neuroprotective Effects ◽  
Concentration Dependent Manner ◽  
Fura 2 ◽  
Glutamate Neurotoxicity

1. Cell-permeant Ca2+ chelators such as 1,2-bis-(2-amino-phenoxy)ethane- N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM) protect neurons against excitotoxic and ischemic neuronal injury in vitro and in vivo. Here we provide the first steps toward characterizing the mechanisms by which these agents produce their neuroprotective effects. 2. Cultured mouse spinal neurons were simultaneously loaded with the Ca2+ indicator fura-2 and with one of three permeant chelators derived from the fast Ca2+ buffer BAPTA, or with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid acetoxymethyl ester (EGTA-AM). Adding these chelators did not interfere with the fluorescence spectrum of fura-2 and had no effect on baseline [Ca2+]i. 3. The neurons were challenged with 250 microM L-glutamate for 50 min, producing a marked transient [Ca2+]i increase followed by a decay of [Ca2+]i to a lower “plateau.” About 80% of control neurons succumbed to this excitotoxic insult. Neurons that survived adjusted their plateau [Ca2+]i to lower levels than those that succumbed. 4. Neurons that were pretreated with permeant Ca2+ chelators became more resistant to these neurotoxic challenges. 5. We examined whether this reduction in glutamate neurotoxicity could be related to the given buffer's known Ca2+ affinity (Kd), its Ca2+ binding kinetics, and its ability to attenuate glutamate-induced [Ca2+]i increases. 6. Pretreatment of neurons with BAPTA analogues having Kds ranging from 100 to 3,600 microM 1) attenuated the amplitude and 2) lengthened the time constant describing the rise and decay of the glutamate-evoked [Ca2+]i transient. The magnitude of these effects paralleled the affinity of the chelator for Ca2+. 7. BAPTA-AM and its analogues dramatically attenuated the early neurotoxicity of glutamate, reducing cell deaths by up to 80%. However, in contrast with the graded effects of chelators having different Ca2+ affinities on Ca2+ transients, all BAPTA analogues were equally protective. These protective effects did not relate to the chelators' Ca2+ affinity within a Kd range of 100 nM (for BAPTA) to 3,600 nM (for 5,5'-dibromo BAPTA). 8. BAPTA-AM protected neurons in a concentration-dependent manner with 50% protection obtained with 10 microM, a concentration having no effect on the [Ca2+]i transient amplitude. 9. EGTA, a slow Ca2+ buffer with a similar Ca2+ affinity to BAPTA produced the same effects as BAPTA on [Ca2+]i transient kinetics. However, it was far less protective than BAPTA. 10. The time course of early glutamate neurotoxicity was altered by the BAPTA analogues, but not EGTA. BAPTA analogues caused a small increase in cell deaths in the first minutes of each experiment, followed by relative sparing from further neurodegeneration. 11. The ability of low Ca2+ affinity chelators such as 5,5'-dibromo BAPTA to protect neurons without markedly attenuating measured [Ca2+]i increases conflicts with the hypothesis that global elevations in [Ca2+]i are responsible for triggering neurotoxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

Protective Effects on Mitochondria and Anti-Aging Activity of Polysaccharides from Cultivated Fruiting Bodies of Cordyceps militaris

2010 ◽  
Vol 38 (06) ◽  
pp. 1093-1106 ◽  
Author(s):  
Xing-Tai Li ◽  
Hong-Cheng Li ◽  
Chun-Bin Li ◽  
De-Qiang Dou ◽  
Ming-Bo Gao
Keyword(s):  
Hydroxyl Radicals ◽  
Cordyceps Militaris ◽  
Mitochondrial Swelling ◽  
Dependent Manner ◽  
Protective Effects ◽  
Fruiting Bodies ◽  
Concentration Dependent Manner ◽  
Mitochondrial Injury

Cordyceps militaris (L.) Link is an entomopathogenic fungus parasitic to Lepidoptera larvae, and is widely used as a folk tonic or invigorant for longevity in China. Although C. militaris has been used in traditional Chinese medicine for millennia, there is still a lack convincing evidence for its anti-aging activities. This study was performed to investigate the effects of polysaccharides from cultivated fruiting bodies of C. militaris (CMP) on mitochondrial injury, antioxidation and anti-aging activity. Fruiting bodies of C. militaris were cultivated artificially under optimized conditions. The spectrophotometric method was used to measure thiobarbituric acid reactive substances (TBARS), mitochondrial swelling, and activities of scavenging superoxide anions in vitro. D-galactose (100 mg/kg/day) was injected subcutaneously into back of the neck of mice for 7 weeks to induce an aging model. The effects of CMP on the activities of catalase (CAT), surperoxide dismutase (SOD), glutathione peroxidase (GPx) and anti-hydroxyl radicals were assayed in vivo using commercial monitoring kits. The results showed that CMP could inhibit mitochondrial injury and swelling induced by Fe2+ -L-Cysteine in a concentration- dependent manner and it also had a significant superoxide anion scavenging effect. Moreover, the activities of CAT, SOD, GPx and anti-hydroxyl radicals in mice liver were increased significantly by CMP. These results indicate that CMP protects mitochondria by scavenging reactive oxygen species (ROS), inhibiting mitochondrial swelling, and increasing the activities of antioxidases. Therefore, CMP may have pharmaceutical values for mitochondrial protection and anti-aging. CMP was the major bioactive component in C. militaris.

Reversal of Anticoagulation as Assessed by Thrombin Generation Measurement.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 876-876
Author(s):  
Alex Gatt ◽  
Joost van Veen ◽  
Peter Cooper ◽  
Steve Kitchen ◽  
Michael Makris
Keyword(s):  
Thrombin Generation ◽  
Fresh Frozen Plasma ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Protamine Sulphate ◽  
Reversal Agents ◽  
Time To Peak ◽  
High Doses ◽  
Vitro Effect

Abstract Antidotes to the ever-growing number of anticoagulants are always desirable in order to placate bleeding in emergencies. In general, the older anticoagulants like coumarins and unfractionated heparin (UFH) have proven reversal agents, whereas the newer ones do not. We studied the in vitro effect of 5 different heparinoids (UFH, Tinzaparin, Enoxaparin, Fondaparinux and Danaparoid) on the calibrated automated thrombogram. The assay uses a fluorogenic substrate that is cleaved by the thrombin formed after the addition of plasma to 5pM tissue factor, 4μM phospholipids and calcium chloride. We investigated all the parameters generated by dedicated software (Thrombinoscope™) ie the lag time (LT), the time to peak (ttpeak), the endogenous thrombin potential (ETP) and the peak thrombin. All the five anticoagulants tested inhibited thrombin generation (TG) in a concentration dependent manner. We subsequently analysed the in vitro effect of different concentrations of six potential reversal agents on correcting TG parameters of maximally inhibited plasma for each anticoagulant. These were protamine sulphate at 2.5, 5 & 8μg/ml, activated FVIIa (Novoseven®) at 5, 10 & 50μg/ml, FEIBA® at 0.5,1 & 2U/ml, Beriplex® at 0.3, 0.6 & 1.2U/ml, Prothromplex® TIM4 at 0.4, 0.8 & 1.8U/ml and fresh frozen plasma (FFP) at 250, 500 & 750μl/ml. The three concentrations reflect the recommended therapeutic doses for each agent together with lower and higher doses than normally used. As predicted, UFH (final concentration 0.527U/ml) was completely reversed with a standard protamine concentration of 5μg/ml. However, the highest dose of protamine gave slightly lower TG, indicating that higher concentrations of protamine sulphate can have a paradoxical ‘anticoagulant’ effect. High doses of FEIBA (2U/ml) and FVIIa (50μg/ml) restored ~50% of thrombin generation parameters. Tinzaparin (at 1antiXaUnit/ml) was also completely neutralised by protamine. However, a higher concentration of 8μg/ml protamine was required. This effect was not seen with Enoxaparin with this higher concentration of protamine reversing only ~40% of the ETP, 21% of the peak thrombin, 71% of ttpeak and 72% of the LT. There was no positive effect of protamine on Fondaparinux (3μg/ml) and Danaparoid (1antiXa U/ml)-treated plasma. Whereas Danaparoid seemed relatively resistant to all six reversal agents, Fondaparinux effect was completely neutralised by FVIIa at concentrations between 10–50μg/ml. This study highlights the differences in neutralisation of different low molecular weight heparins and UFH. In particular, Tinzaparin was much more readily reversed with protamine sulphate than Enoxaparin. It also indicates that high doses of FVIIa could completely reverse Fondaparinux anticoagulation.

scholarly journals In vitro Activity of Ozoroa pulcherrima Schweinf. Extracts and Fractions on Schistosoma mansoni Cercariae and Adult Worms

2020 ◽  
pp. 17-30
Author(s):  
Nestor Gipwe Feussom ◽  
Hermine Boukeng Jatsa ◽  
Mérimé Christian Kenfack ◽  
Emilienne Tienga Nkondo ◽  
Ulrich Membe Femoe ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Methanolic Extract ◽  
Lower Abdominal Pain ◽  
In Vitro Assays ◽  
Dependent Manner ◽  
In Vitro Activity ◽  
Concentration Dependent Manner ◽  
Methanolic Extracts ◽  
Effective Drugs

Aims: Continuous attempts are being made to develop new and more effective drugs for the treatment of schistosomiasis. Ozoroa pulcherrima Schweinf. is a medicinal plant used in Africa for the treatment of dysmenorrhea, lower abdominal pain, dystocia and intestinal helminthiasis. This study provides findings on the cercaricidal and schistosomicidal activity of extracts and fractions of Ozoroa pulcherrima in in vitro assays. Methodology: The aqueous and methanolic extracts from Ozoroa pulcherrima root parts (62.5 – 2000 µg/mL), as well as the methanol derived fractions (n-hexane and ethyl acetate: 31.25 – 1000 µg/mL) were tested on cercariae and adult worms of Schistosoma mansoni. Niclosamide-olamine 5% (1 µg/mL) and praziquantel (10 µg/mL) were respectively used as reference drugs. During the assays, the mortality of cercariae after 2 hours, and adult worms’ mobility and mortality after 48 hours of incubation were evaluated. Results: Ozoroa pulcherrima extracts and fractions significantly increased cercariae and worm mortality in a concentration-dependent manner. The methanolic extract was the most active on cercariae with a LC50of 20.65 µg/mL after 30 minutes, while the n-hexane fraction was the most active on worm with a LC50 of 79.54 μg/mL (65.58 – 96.47 μg/mL) after 48 hours. Significant reduction of motor activity (18.47 to 100%) was recorded for surviving worms incubated in different concentrations of the extracts and fractions. Conclusion: This study proves that Ozoroa pulcherrima extracts and fractions have cercaricidal and schistosomicidal activities. Ozoroa pulcherrima may have great potential as an anti-schistosomal agent for further research.

scholarly journals Protective Effects of Aqueous Extracts of Flos lonicerae Japonicae against Hydroquinone-Induced Toxicity in Hepatic L02 Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yanfang Gao ◽  
Huanwen Tang ◽  
Liang Xiong ◽  
Lijun Zou ◽  
Wenjuan Dai ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Viability ◽  
Dependent Manner ◽  
Aqueous Extracts ◽  
Protective Effects ◽  
Concentration Dependent Manner ◽  
Flos Lonicerae ◽  
L02 Cells ◽  
Flos Lonicerae Japonicae

Hydroquinone (HQ) is widely used in food stuffs and is an occupational and environmental pollutant. Although the hepatotoxicity of HQ has been demonstrated both in vitro and in vivo, the prevention of HQ-induced hepatotoxicity has yet to be elucidated. In this study, we focused on the intervention effect of aqueous extracts of Flos lonicerae Japonicae (FLJ) on HQ-induced cytotoxicity. We demonstrated that HQ reduced cell viability in a concentration-dependent manner by administering 160 μmol/L HQ for 12 h as the positive control of cytotoxicity. The aqueous FLJ extracts significantly increased cell viability and decreased LDH release, ALT, and AST in a concentration-dependent manner compared with the corresponding HQ-treated groups in hepatic L02 cells. This result indicated that aqueous FLJ extracts could protect the cytotoxicity induced by HQ. HQ increased intracellular MDA and LPO and decreased the activities of GSH, GSH-Px, and SOD in hepatic L02 cells. In addition, aqueous FLJ extracts significantly suppressed HQ-stimulated oxidative damage. Moreover, HQ promoted DNA double-strand breaks (DSBs) and the level of 8-hydroxy-2′-deoxyguanosine and apoptosis. However, aqueous FLJ extracts reversed HQ-induced DNA damage and apoptosis in a concentration-dependent manner. Overall, our results demonstrated that the toxicity of HQ was mediated by intracellular oxidative stress, which activated DNA damage and apoptosis. The findings also proved that aqueous FLJ extracts exerted protective effects against HQ-induced cytotoxicity in hepatic L02 cells.

scholarly journals Atheroprotective action of a modified organoselenium compound: in vitro evidence

2016 ◽  
Vol 88 (3 suppl) ◽  
pp. 1953-1965 ◽  
Author(s):  
JADE DE OLIVEIRA ◽  
MARCOS R. STRALIOTTO ◽  
GIANNI MANCINI ◽  
CLAUDIA P. FIGUEIREDO ◽  
ANTÔNIO L. BRAGA ◽  
...  
Keyword(s):  
Foam Cell ◽  
Oxidized Ldl ◽  
Ldl Oxidation ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Protective Effects ◽  
Organoselenium Compound ◽  
Organoselenium Compounds ◽  
Concentration Dependent Manner

ABSTRACT Oxidation of low-density lipoprotein (LDL) has been strongly suggested to play a significant role in the pathogenesis of atherosclerosis. Thus, reducing LDL oxidation is a potential approach to decrease the risk of the atherosclerosis. Organoselenium compounds have demonstrated promising atheroprotective properties in experimental models. Herein, we tested the in vitro atheroprotective capability of a modified organoselenium compound, Compound HBD, in protecting isolated LDL from oxidation as well as foam cells formation. Moreover, the glutathione peroxidase (GPx)-like activity of Compound HBD was analyzed in order to explore the mechanisms related to the above-mentioned protective effects. The Compound HBD in a concentration-dependent manner reduced the Cu2+-induced formation of conjugated dienes. The protein portion from LDL were also protected from Cu2+-induced oxidation. Furthermore, the Compound HBD efficiently decreased the foam cell formation in J774 macrophage cells exposed to oxidized LDL. We found that the atheroprotective effects of this compound can be, at least in part, related to its GPx-like activity. Our findings demonstrated an impressive effect of Compound HBD against LDL-induced toxicity, a further in vivo study to investigate in more detail the antioxidant and antiatherogenic effects of this compound could be considered.

Modifications of cellular responses to lysophosphatidic acid and platelet-activating factor by plasma gelsolin

2007 ◽  
Vol 292 (4) ◽  
pp. C1323-C1330 ◽  
Author(s):  
Teresia M. Osborn ◽  
Claes Dahlgren ◽  
John H. Hartwig ◽  
Thomas P. Stossel
Keyword(s):  
Platelet Activating Factor ◽  
Protective Role ◽  
Actin Binding ◽  
Dependent Manner ◽  
Protective Effects ◽  
Concentration Dependent Manner ◽  
Blood Concentrations ◽  
Plasma Gelsolin

Gelsolin is a highly conserved intracellular actin-binding protein with an extracellular isoform, plasma gelsolin (pGSN). Blood concentrations of pGSN decrease in response to diverse tissue injuries. Depletion of pGSN to critical levels precedes and often predicts complications of injuries such as lung permeability changes and death. Administration of recombinant pGSN ameliorates such complications and reduces mortality in animal models. One proposed mechanism for pGSN's protective effects is that it inhibits inflammatory mediators generated during primary injuries, since pGSN binds bioactive mediators, including lysophospatidic acid (LPA) and endotoxin in vitro. However, no direct evidence in support of this hypothesis has been available. Here we show that recombinant pGSN modestly inhibited LPA-induced P-selectin upregulation by human platelets in the presence of albumin ( P < 0.0001). However, physiologically relevant pGSN concentrations inhibit platelet-activating factor (PAF)-mediated P-selectin expression by up to 77% ( P < 0.0001). pGSN also markedly inhibited PAF-induced superoxide anion (O2−) production of human peripheral neutrophils (PMN) in a concentration-dependent manner ( P < 0.0001). A phospholipid-binding peptide derived from pGSN (QRLFQVKGRR) also inhibited PAF-mediated O2− generation ( P = 0.024). Therefore, pGSN interferes with PAF- and LPA-induced cellular activation in vitro, suggesting a mechanism for the protective role of pGSN in vivo.

scholarly journals Cytoprotective effects of albumin, nitrosated or reduced, in cultured rat pulmonary vascular cells

2011 ◽  
Vol 300 (4) ◽  
pp. L526-L533 ◽  
Author(s):  
Hui-Hua Li ◽  
Jing Xu ◽  
Karla J. Wasserloos ◽  
Jin Li ◽  
Yulia Y. Tyurina ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Methyl Ester ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cellular Respiration ◽  
Dependent Manner ◽  
Protective Effects ◽  
Limited Information ◽  
Concentration Dependent Manner ◽  
Sodium Hydrosulfide

S-nitrosoalbumin (SNO-Alb) has been shown to be an efficacious cytoprotective molecule in acute lung injury, as well as ischemia-reperfusion injury in heart and skeletal muscle. Nonetheless, limited information is available on the cellular mechanism of such protection. Accordingly, we investigated the protective effects of SNO-Alb [ and its denitrosated congener, reduced albumin (SH-Alb) ] on tert-butyl hydroperoxide (tBH)-mediated cytotoxicity in cultured rat pulmonary microvascular endothelial cells (RPMEC), as well as hydrogen sulfide (H2S)-mediated cytotoxicity in rat pulmonary artery smooth muscle cells (RPASMC). We noted that tBH caused a concentration-dependent necrosis in RPMEC, and pretreatment of RPMEC with SNO-Alb dose-dependently decreased the sensitivity of these cells to tBH. A component of SNO-Alb cytoprotection was sensitive to NG-nitro-l-arginine methyl ester and was associated with activation of endothelial nitric oxide synthase (eNOS), phenomena that could be reproduced with pretreatment with SH-Alb. Exogenous H2S caused concentration-dependent apoptosis in RPASMC due to activation of ERK1/2 and p38, as well as downregulation of Bcl-2. Pretreatment with SNO-Alb reduced H2S-mediated apoptosis in a concentration-dependent manner that was associated with SNO-Alb-mediated inhibition of activation of ERK1/2 and p38. Pretreatment with SNO-Alb reduced toxicity of 1 mM sodium hydrosulfide in an NG-nitro-l-arginine methyl ester-sensitive fashion in RPASMC that expressed gp60 and neuronal NOS and was capable of transporting fluorescently labeled SH-Alb. Therefore, SNO-Alb is cytoprotective against models of oxidant-induced necrosis (tBH) and inhibitors of cellular respiration and apoptosis (H2S) in both pulmonary endothelium and smooth muscle, respectively, and a component of such protection can be attributed to a SH-Alb-mediated activation of constitutive NOS.

scholarly journals Investigation of Hepatoprotective and Antioxidant Activity of Celosia argentea against Tissue Injury Caused by Rifampicin Administration

2019 ◽  
pp. 1-11 ◽  
Author(s):  
Abiodun Olusoji Owoade ◽  
Adewale Adetutu ◽  
Olubukola Sinbad Olorunnisola ◽  
Olufemi Ogundeji Ogundipe
Keyword(s):  
Tissue Injury ◽  
Radical Scavenging ◽  
Hdl Cholesterol ◽  
Dependent Manner ◽  
Protective Effects ◽  
Sod Activity ◽  
Concentration Dependent Manner ◽  
Celosia Argentea ◽  
Liver And Kidney

This study evaluated the antioxidant and possible protective effects of Celosia argentea against tissue injury caused by rifampicin administration. The antioxidant property of the aqueous extract of C. argentea was assessed in-vitro using 2,2-Diphenyl-1- picrylhydrazyl (DPPH), and 2,2-azino-bis (3-ethylbenzthiazoline-6-sufonic acid) (ABTS) assays. The results obtained revealed the free radical scavenging ability of the extract against the radicals in a concentration-dependent manner. Administration of rifampicin to rats for 28 days induced a significant increase in the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and increase cholesterol levels in the plasma, liver and kidney while HDL cholesterol was decreased. It also elevated the levels of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activities in the liver and kidney. However, co-administration of C. argentea extract to rifampicin treated rats significantly reversed all these rifampicin induced changes. The levels of AST, ALT, ALP and cholesterol in the plasma, liver and kidney were decreased while HDL cholesterol level was increased. In addition, SOD activity was elevated while MDA was depressed when compared to the rifampicin treated rats. The extract of C. argentea was found to be rich in phenolic content and was proved to have no toxic effects on rats when administered alone to normal rats at a dose level of 400mg/kg/day. This study demonstrated that C. argentea leaf extract ameliorates rifampicin-induced hepatotoxicity and could be exploited in the management of hepatotoxic effect associated with rifampicin treatment.

scholarly journals Nucleus pulposus cell senescence is alleviated by resveratrol through regulating the ROS/NF-κB pathway under high-magnitude compression

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Yanhai Jiang ◽  
Guozhang Dong ◽  
Yeliang Song
Keyword(s):  
Nucleus Pulposus ◽  
Bone Matrix ◽  
Nucleus Pulposus Cell ◽  
Cell Senescence ◽  
Ros Generation ◽  
Dependent Manner ◽  
Protective Effects ◽  
Concentration Dependent Manner ◽  
High Magnitude

Mechanical overloading is a risk factor of disc degeneration. Studies have demonstrated that resveratrol helps to maintain the disc cell’s healthy biology. The present study aims to investigate whether resveratrol can suppress mechanical overloading-induced nucleus pulposus (NP) cell senescence in vitro and the potential mechanism. The isolated rat NP cells were seeded in the decalcified bone matrix (DBM) and cultured under non-compression (control) and compression (20% deformation, 1.0 Hz, 6 h/day) for 5 days using the mechanically active bioreactor. The resveratrol (30 and 60 μM) was added into the culture medium of the compression group to investigate its protective effects against the NP cell senescence. NP cell senescence was evaluated by cell proliferation, cell cycle, senescence-associated β-galactosidase (SA-β-Gal) activity, telomerase (TE) activity, and gene expression of the senescence markers (p16 and p53). Additionally, the reactive oxygen species (ROS) content and activity of the NF-κB pathway were also analyzed. Compared with the non-compression group, the high-magnitude compression significantly promoted NP cell senescence, increased ROS generation and activity of the NF-κB pathway. However, resveratrol partly attenuated NP cell senescence, decreased ROS generation and activity of the NF-κB pathway in a concentration-dependent manner under mechanical compression. Resveratrol can alleviate mechanical overloading-induced NP cell senescence through regulating the ROS/NF-κB pathway. The present study provides that resveratrol may be a potential drug for retarding mechanical overloading-induced NP cell senescence.

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