scholarly journals Effects of Propentofylline on Hypoxia—Hypoglycemia-Induced Calcium Accumulation in Gerbil Hippocampal Slices

1992 ◽  
Vol 12 (2) ◽  
pp. 301-305 ◽  
Author(s):  
Fumito Kadoya ◽  
Akira Mitani ◽  
Tatsuru Arai ◽  
Kiyoshi Kataoka
Keyword(s):  
Cerebral Ischemia ◽  
Intracellular Calcium ◽  
Neuronal Damage ◽  
Hippocampal Slices ◽  
Dependent Manner ◽  
Protective Effects ◽  
Calcium Accumulation ◽  
Xanthine Derivative ◽  
Acute Increase ◽  
Dose Dependent

The xanthine derivative propentofylline (HWA 285) has been reported to show protective effects against neuronal damage induced by cerebral ischemia. In the present study, microfluorometry was used to investigate the effect of propentofylline on the hypoxia–hypoglycemia-induced intracellular calcium accumulation in gerbil hippocampal slices. When slices were superfused with hypoxic–hypoglycemic medium that did not contain propentofylline, an acute increase in calcium accumulation was detected 75–200 s (mean latency of 123 s) after the beginning of hypoxia–hypoglycemia. When slices were superfused with hypoxic–hypoglycemic mediums that contained 10 μ M, 100 μ M, and 1 m M propentofylline, the latency of the acute increase in calcium accumulation was prolonged in all subregions of the hippocampus in a dose-dependent manner: mean latencies in field CA1 were 146, 168, and 197 s after hypoxia–hypoglycemia, respectively. This retardation in calcium accumulation may be involved in the mechanisms by which propentofylline diminishes ischemic injury.

scholarly journals Necroptosis protects against exacerbation of acute pancreatitis

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Michittra Boonchan ◽  
Hideki Arimochi ◽  
Kunihiro Otsuka ◽  
Tomoko Kobayashi ◽  
Hisanori Uehara ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Necrotizing Pancreatitis ◽  
Neutrophil Infiltration ◽  
Dependent Manner ◽  
Protective Effects ◽  
Interacting Protein ◽  
Inflammatory Conditions ◽  
Edematous Pancreatitis ◽  
Genetic Deletion ◽  
Dose Dependent

AbstractThe sensing of various extrinsic stimuli triggers the receptor-interacting protein kinase-3 (RIPK3)-mediated signaling pathway, which leads to mixed-lineage kinase-like (MLKL) phosphorylation followed by necroptosis. Although necroptosis is a form of cell death and is involved in inflammatory conditions, the roles of necroptosis in acute pancreatitis (AP) remain unclear. In the current study, we administered caerulein to Ripk3- or Mlkl-deficient mice (Ripk3−/− or Mlkl−/− mice, respectively) and assessed the roles of necroptosis in AP. We found that Ripk3−/− mice had significantly more severe pancreatic edema and inflammation associated with macrophage and neutrophil infiltration than control mice. Consistently, Mlkl−/− mice were more susceptible to caerulein-induced AP, which occurred in a time- and dose-dependent manner, than control mice. Mlkl−/− mice exhibit weight loss, edematous pancreatitis, necrotizing pancreatitis, and acinar cell dedifferentiation in response to tissue damage. Genetic deletion of Mlkl resulted in downregulation of the antiapoptotic genes Bclxl and Cflar in association with increases in the numbers of apoptotic cells, as detected by TUNEL assay. These findings suggest that RIPK3 and MLKL-mediated necroptosis exerts protective effects in AP and caution against the use of necroptosis inhibitors for AP treatment.

scholarly journals Curcumin Protects Neuron against Cerebral Ischemia-Induced Inflammation through Improving PPAR-Gamma Function

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Zun-Jing Liu ◽  
Wei Liu ◽  
Lei Liu ◽  
Cheng Xiao ◽  
Yu Wang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Neuronal Damage ◽  
Infarct Volume ◽  
Critical Role ◽  
Ischemic Injury ◽  
Ppar Gamma ◽  
Neurological Deficits ◽  
Protective Effects ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic

Cerebral ischemia is the most common cerebrovascular disease worldwide. Recent studies have demonstrated that curcumin had beneficial effect to attenuate cerebral ischemic injury. However, it is unclear how curcumin protects against cerebral ischemic injury. In the present study, using rat middle cerebral artery occlusion model, we found that curcumin was a potent PPARγagonist in that it upregulated PPARγexpression and PPARγ-PPRE binding activity. Administration of curcumin markedly decreased the infarct volume, improved neurological deficits, and reduced neuronal damage of rats. In addition, curcumin suppressed neuroinflammatory response by decreasing inflammatory mediators, such as IL-1β, TNF-α, PGE2, NO, COX-2, and iNOS induced by cerebral ischemia of rats. Furthermore, curcumin suppressed IκB degradation that was caused by cerebral ischemia. The present data also showed that PPARγinteracted with NF-κB-p65 and thus inhibited NF-κB activation. All the above protective effects of curcumin on cerebral ischemic injury were markedly attenuated by GW9662, an inhibitor of PPARγ. Our results as described above suggested that PPARγinduced by curcumin may play a critical role in protecting against brain injury through suppression of inflammatory response. It also highlights the potential of curcumin as a therapeutic agent against cerebral ischemia.

Presynaptic Modulation of Synaptic Transmission by Pregnenolone Sulfate as Studied by Optical Recordings

2005 ◽  
Vol 94 (6) ◽  
pp. 4131-4144 ◽  
Author(s):  
Ling Chen ◽  
Masahiro Sokabe
Keyword(s):  
Synaptic Transmission ◽  
Glutamate Release ◽  
Hippocampal Slices ◽  
Receptor Activation ◽  
Optical Recording ◽  
Perforant Path ◽  
Dependent Manner ◽  
Pregnenolone Sulfate ◽  
Voltage Sensitive Dyes ◽  
Dose Dependent

The effects of pregnenolone sulfate (PREGS), a putative neurosteroid, on the transmission of perforant path–granule cell synapses were investigated with an optical recording technique in rat hippocampal slices stained with voltage-sensitive dyes. Application of PREGS to the bath solution resulted in an acute augmentation of EPSP in a dose-dependent manner. The PREGS effect was dependent on the extracellular Ca2+ concentration ([Ca2+]o), but independent of NMDA receptor activation. PREGS caused a decrease in paired-pulse facilitation, which implies that PREGS positively modulates presynaptic neurotransmitter releases. Firmer support for this mechanism was that PREGS augmented the synaptically induced glial depolarization (SIGD) that reflects the activity of electrogenic glutamate transporters in glial cells during the uptake of released glutamate. The selective α7nAChR antagonist α-BGT or MLA prevented the SIGD increase by PREGS. Furthermore DMXB, a selective α7nAChR agonist, mimicked the PREGS effect on SIGD and antagonized the effect of PREGS. The presynaptic effect of PREGS was partially attenuated by the L-type Ca2+ channel (VGCC) blocker nifedipine. Based on these findings, we proposed a novel mechanism underlying the facilitated synaptic transmission by PREGS: this neurosteroid sensitizes presynaptic α7nAChR that is followed by an activation of L-type VGCC to increase the presynaptic glutamate release.

scholarly journals Hepatoprotective effects of Sapium sebiferum in paracetamol-induced liver injury

2015 ◽  
Vol 10 (2) ◽  
pp. 393 ◽  
Author(s):  
Liaqat Hussain ◽  
Muhammad Sajid Hamid Akash ◽  
Madeha Tahir ◽  
Kanwal Rehman
Keyword(s):  
Liver Injury ◽  
Serum Levels ◽  
Therapeutic Effects ◽  
Sapium Sebiferum ◽  
Dependent Manner ◽  
Protective Effects ◽  
Drug Induced ◽  
Standard Drug ◽  
Hepatoprotective Effects ◽  
Dose Dependent

<span><em>Sapium sebiferum</em> leaves were used to determine its hepatoprotective effects against paracetamol-induced hepatotoxicity in mice. A dose dependent study was conducted using two different doses (200 mg/kg and 400 mg/kg) of the extract of </span><em>S. sebiferum</em><span> against toxic effects of paracetamol (500 mg/kg) in experimental animal model. Silymarin (50 mg/kg) was used as standard drug to compare therapeutic effects of </span><em>S. sebiferum</em><span> with control and paracetamol-treated groups. Paracetamol significantly increased the serum levels of liver enzyme markers like alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin. The extract showed protective effects by normalizing the liver enzymes markers in a dose dependent manner. Histopathological results confirmed the hepatoprotective effects of leaves of </span><em>S. sebiferum</em><span>. We conclude that leaves of </span><em>S. sebiferum</em><span> have strong hepatoprotective effects against paracetamol-induced liver injury and can be used in liver injuries caused by drug-induced toxicity.</span>

Neuronal damage and calcium accumulation following repeated brief cerebral ischemia in the gerbil

1990 ◽  
Vol 528 (1) ◽  
pp. 114-122 ◽  
Author(s):  
Tsutomu Araki ◽  
Hiroyuki Kato ◽  
Kyuya Kogure
Keyword(s):  
Cerebral Ischemia ◽  
Neuronal Damage ◽  
Calcium Accumulation

Invited Review: Effects of flow on vascular endothelial intracellular calcium signaling of rat aortas ex vivo

2000 ◽  
Vol 89 (4) ◽  
pp. 1657-1662 ◽  
Author(s):  
Chauying J. Jen ◽  
Shuo-Ju Jhiang ◽  
Hsiun-Ing Chen
Keyword(s):  
Shear Stress ◽  
Intracellular Calcium ◽  
Calcium Influx ◽  
Ex Vivo ◽  
Flow Chamber ◽  
Shear Stresses ◽  
Dependent Manner ◽  
Intracellular Calcium Signaling ◽  
Flow Effects ◽  
Dose Dependent

To study the effects of flow on in situ endothelial intracellular calcium concentration ([Ca2+]i) signaling, rat aortic rings were loaded with fura 2, mounted on a tissue flow chamber, and divided into control and flow-pretreated groups. The latter was perfused with buffer at a shear stress of 50 dyns/cm2 for 1 h. Endothelial [Ca2+]i responses to ACh or shear stresses were determined by ratio image analysis. Moreover, ACh-induced [Ca2+]i elevation responses were measured in a calcium-free buffer, or in the presence of SKF-96365, to elucidate the role of calcium influx in the flow effects. Our results showed that 1) ACh increased endothelial [Ca2+]i in a dose-dependent manner, and these responses were incremented by flow-pretreatment; 2) the differences in ACh-induced [Ca2+]i elevation between control and flow-pretreated groups were abolished by SKF-96365 or by Ca2+-free buffer; and 3) in the presence of 10−5 M ATP, shear stress induced dose-dependent [Ca2+]i elevation responses that were not altered by flow-pretreatment. In conclusion, flow-pretreatment augments the ACh-induced endothelial calcium influx in rat aortas ex vivo.

scholarly journals Physicochemical Properties of Collagen from Acaudina Molpadioides and Its Protective Effects against H2O2-Induced Injury in RAW264.7 Cells

Marine Drugs ◽  
2020 ◽  
Vol 18 (7) ◽  
pp. 370
Author(s):  
Jie Li ◽  
Yan Li ◽  
Yuyao Li ◽  
Zuisu Yang ◽  
Huoxi Jin
Keyword(s):  
Sulfonic Acid ◽  
Antioxidant Activities ◽  
Physicochemical Characterization ◽  
Raw264.7 Cells ◽  
Composition Analysis ◽  
Dependent Manner ◽  
Protective Effects ◽  
Dose Dependent ◽  
Zeta Potential Analysis ◽  
Improve Cell Viability

Collagen is a promising biomaterial used in the beauty and biomedical industries. In this study, the physicochemical characterization, antioxidant activities, and protective effects against H2O2-induced injury of collagen isolated from Acaudina molpadioides were investigated. The amino acid composition analysis showed that the collagen was rich in glycine (Gly), alanine (Ala), and glutamic acid (Glu), but poor in tyrosine (Tyr) and phenylalanine (Phe). Zeta potential analysis revealed that the isoelectric point (pI) of collagen from Acaudina molpadioides was about 4.25. It possessed moderate scavenging activities of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2’-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals in a dose-dependent manner. In addition, the collagen was able to effectively improve cell viability and morphology, inhibit the production of Malondialdehyde (MDA), and increase the activities of Superoxide Dismutase (SOD) and Glutathione Peroxidase (GSH-Px) in cultured RAW264.7 cells, resulting in a protective effect against H2O2-induced injury. Overall, the results showed that collagen extracted from A. molpadioides has promising prospects in the beauty and cosmetics industries.

scholarly journals NEMO-Binding Domain Peptide Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting the NF-κB Signaling Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Jianhua Huang ◽  
Li Li ◽  
Weifeng Yuan ◽  
Linxin Zheng ◽  
Zhenhui Guo ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Binding Domain ◽  
Dependent Manner ◽  
Protective Effects ◽  
Lps Challenge ◽  
Domain Peptide ◽  
Nemo Binding Domain ◽  
Dose Dependent

The aim of the present study is to investigate the protective effects and relevant mechanisms exerted by NEMO-binding domain peptide (NBD) against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. The ALI model was induced by intratracheally administered atomized LPS (5 mg/kg) to BABL/c mice. Half an hour before LPS administration, we treated the mice with increasing concentrations of intratracheally administered NBD or saline aerosol. Two hours after LPS administration, each group of mice was sacrificed. We observed that NBD pretreatment significantly attenuated LPS-induced lung histopathological injury in a dose-dependent manner. Western blotting established that NBD pretreatment obviously attenuated LPS-induced IκB-αand NF-κBp65 activation and NOX1, NOX2, and NOX4 overexpression. Furthermore, NBD pretreatment increased SOD and T-AOC activity and decreased MDA levels in lung tissue. In addition, NBD also inhibited TNF-αand IL-1βsecretion in BALF after LPS challenge. In conclusion, NBD protects against LPS-induced ALI in mice.

scholarly journals Proteomic Assessment of iTRAQ-Based NaoMaiTong in the Treatment of Ischemic Stroke in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Kening Li ◽  
Minghua Xian ◽  
Chi Chen ◽  
Shengwang Liang ◽  
Lei Chen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Cerebral Infarction ◽  
Western Blot ◽  
Stress Responses ◽  
Neuronal Damage ◽  
Interaction Analysis ◽  
Protective Effects ◽  
Cellular Mechanisms ◽  
Altered Expression

Background. NaoMaiTong (NMT) is widely used in the treatment of cerebral ischemia but the molecular details of its beneficial effects remain poorly characterized. Materials and Methods. In this study, we used iTRAQ using 2D LC-MS/MS technology to investigate the cellular mechanisms governing the protective effects of NMT. The transient middle cerebral artery occlusion (MCAO) rat model was established and evaluated. The degree of cerebral ischemia was assessed through scoring for nerve injury symptoms and through the assessment of the areas of cerebral infarction. Brain tissues were subjected to analysis by iTRAQ. High-pH HPLC and RSLC-MS/MS analysis were performed to detect differentially expressed proteins (DEPs) between the treatment groups (Sham, MCAO, and NMT). Bioinformatics were employed for data analysis and DEPs were validated by western blot. Results. The results showed that NMT offers protection to the neurological damage caused by MCAO and was found to reduce the areas of cerebral infarction. We detected 3216 DEPs via mass spectrometry. Of these proteins, 21 displayed altered expression following NMT intervention. These included DEPs involved in translation, cell cycle regulation, cellular nitrogen metabolism, and stress responses. Pathway analysis revealed seven key DEPs that were enriched in ribosomal synthesis pathways, tight junction formation, and regulation of the actin cytoskeleton. According to protein-protein interaction analysis, RPL17, Tuba, and Rac1 were affected by NMT treatment, which was validated by western blot analysis. Discussion. We therefore identify new pharmacodynamic mechanisms of NMT for the prevention and treatment of ischemic stroke. These DEPs reveal new targets to prevent ischemic stroke induced neuronal damage.

Sign in / Sign up

Export Citation Format

Share Document