Abstract：
:CHF5074 is a non-steroidal anti-inflammatory derivative holding disease-modifying potential for the treatment of Alzheimer's disease. The aim of the present study was to characterize the electrophysiological and metabolic profile of CHF5074 in the hippocampus. Electrophysiological recordings show that CHF5074 inhibits in a dose-dependent manner the current-evoked repetitive firing discharge in CA1 pyramidal neurons. This result is paralleled by a dose-dependent reduction of field excitatory post-synaptic potentials with no effect on the paired-pulse ratio. The effects of CHF5074 were not mediated by AMPA or NMDA receptors, since the inward currents induced by local applications of AMPA and NMDA remained constant in the presence of this compound. We also suggest a possible activity of CHF5074 on ASIC1a receptor since ASIC1a-mediated current, evoked by application of a pH 5.5 solution, is reduced by pretreatment with this compound. Moreover, we demonstrate that CHF5074 treatment is able to counteract in hippocampal slices the OGD-induced increase in alanine, lactate and acetate levels. Finally, CHF5074 significantly reduced the apoptosis in hippocampal neurons exposed to OGD, as revealed by cleaved-caspase-3 immunoreactivity and TUNEL staining. Overall, the present work identifies novel mechanisms for CHF5074 in reducing metabolic acidosis, rendering this compound potentially useful also in conditions of brain ischemia.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Mango D,Barbato G,Piccirilli S,Panico MB,Feligioni M,Schepisi C,Graziani M,Porrini V,Benarese M,Lanzillotta A,Pizzi M,Pieraccini S,Sironi M,Blandini F,Nicoletti F,Mercuri NB,Imbimbo BP,Nisticò Rdoi
10.1016/j.phrs.2014.02.010subject
Has Abstractpub_date
2014-03-01 00:00:00pages
83-90eissn
1043-6618issn
1096-1186pii
S1043-6618(14)00023-1journal_volume
81pub_type
杂志文章abstract：:Hepatitis E virus (HEV) is the most common cause of viral hepatitis worldwide. Genotypes 1 and 2 (GT1 and GT2) are mainly present in developing countries, while GT3 and GT4 are prevalent in developed and high-income countries. In the majority of cases, HEV causes a self-limiting hepatitis. GT3 and GT4 can be responsib...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2018.02.030
更新日期：2018-04-01 00:00:00
abstract：:Serotonin (5-HT) is present in high concentration in enterochromaffin cells throughout the gastrointestinal tract, where it plays a very important role, being involved, e.g., in peristaltic and secretory reflexes in response to chemical or mechanical stimuli of the gut. Intestinal 5-HT is inactivated by metabolic degr...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2006.04.005
更新日期：2006-08-01 00:00:00
abstract：:Flt3 is expressed by early myeloid and lymphoid progenitor cells and it regulates the proliferation and differentiation of hematopoietic cells. Flt3 is activated by the Flt3 ligand, the monomeric form of which is a polypeptide of about 200 amino acid residues. Both membrane-associated and soluble Flt3 ligands, which a...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2020.104725
更新日期：2020-05-01 00:00:00
abstract：:Alzheimer's disease (AD) is regarded as a progressive and devastating neurodegenerative disorder. In aged individuals, it is the most prevalent cause of dementia and is characterized by gradual loss of cognitive functions. In the last decade, numerous research works were undertaken to investigate the pathogenesis of A...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2017.11.028
更新日期：2018-03-01 00:00:00
abstract：:Familial hypercholesterolemia (FH) is a genetic autosomal dominant disorder caused by an impaired receptor-mediated low-density lipoprotein (LDL) removal from the circulation, mainly due to disruptive autosomal co-dominant mutations in the LDL receptor (LDLr) gene, but also less frequently in the apolipoprotein B100 (...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2019.03.016
更新日期：2019-05-01 00:00:00
abstract：:The aqueous extract from aerial parts of Artemisia copa Phil. (Compositae), was evaluated for antinociceptive activity using writhing, formalin, and hot-plate tests in mice. A dose-related antinociceptive response was obtained in the writhing test at doses of 500 and 1000 mg/kg p.o. (percentage of inhibition 23.3 and ...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2003.12.016
更新日期：2004-07-01 00:00:00
abstract：:Antidepressants, especially tricyclic agents (TCAs), are increasingly used in geriatric patients since depression is a common mood disorder in the elderly and the size of elderly population is increasing. Notwithstanding the importance of kinetics to better use of drugs, its study in the elderly (regarding TCAs) is no...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/1043-6618(90)90739-z
更新日期：1990-01-01 00:00:00
abstract：UNLABELLED:The purpose of this study was an attempt to extrapolate favorable observations on the effects of magnesium on platelets and haemostasis from animal models to humans. Intravenous magnesium in the treatment of acute myocardial infarction has been tested in several large clinical trials and remains controversia...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1997.0212
更新日期：1997-07-01 00:00:00
abstract：:The aminosteroid derivative RM-133 is an effective anticancer molecule for which proof of concept has been achieved in several mouse xenograph models (HL-60, MCF-7, PANC-1 and OVCAR-3). To promote this new family of molecules toward a clinical phase 1 trial, the mechanism of action governing the anticancer properties ...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2017.12.024
更新日期：2018-02-01 00:00:00
abstract：:The synergistic protective effect of nicorandil (KATP channel opener) and amlodipine (calcium channel blocker) on mitochondrial respiration and mitochondrial lipid contents were examined on isoproterenol-induced myocardial infarction in rats. The rats given isoproterenol (150 mg kg(-1) daily, i.p.) for 2 days showed s...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043-6618(03)00223-8
更新日期：2003-12-01 00:00:00
abstract：:Diabetes is a chronic metabolic disease characterized by hyperglycemia and several associated biochemical abnormalities. Diabetes leads to multiorgan complications that collectively reduce life expectancy. Hematopoietic stem cells (HSCs) are nested within bone marrow (BM) niches whence they can be mobilized to the per...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2018.07.017
更新日期：2018-09-01 00:00:00
abstract：:Tissue subjected to a period of ischemia undergoes functional and morphological damage that increases during the reperfusion phase. In this study, the protective effect of aprotinin, which is a protease inhibitor, was assessed in a rabbit unilateral renal ischemia-reperfusion (I/R) model. New Zealand rabbits, weighing...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.2001.0902
更新日期：2001-12-01 00:00:00
abstract：:Gossypol, a cottonseed extract, has been shown to have antiproliferative activity in a variety of cancer cell lines. The objective of this study was to determine the inhibitory effects of gossypol on cell proliferation. Five human carcinoma cell lines were evaluated including endometrial (RL95-2), ovarian (SKOV-3), me...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s104366180200230x
更新日期：2002-12-01 00:00:00
abstract：:Despite the exploration of a large number of disparate drugs in animal models and clinical trials, no pharmacological intervention, with the exception of aggressive lipid lowering therapy has reduced late vein graft failure in man. The importance of devising more effective strategies is exemplified by the enormous eco...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2010.10.018
更新日期：2011-06-01 00:00:00
abstract：:In the present study, an attempt has been made to elucidate the role of alpha 2-adrenoceptors in reserpine-induced emesis in pigeons. Reserpine was found to induce dose-dependent emesis and a 500 micrograms kg-1 dose was found to be the 100% emetic dose. alpha 2-adrenoceptor agonists clonidine and alpha-methylnoradren...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/1043-6618(94)80060-x
更新日期：1994-05-01 00:00:00
abstract：:Corticosteroids are shown to have deleterious effects on wound healing for various tissues. Arginine metabolism and nitric oxide (NO) synthesis play an important role in many aspects of inflammation and wound healing. The study was designed to evaluate the relationship of dexamethasone impaired healing of tracheal ana...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043-6618(02)00130-5
更新日期：2002-09-01 00:00:00
abstract：:The aim of this study was to investigate the effects of manganese chloride on gentamicin-induced nephrotoxicity in rats. Thirty-six adult Wistar Albino rats were divided into six equal groups. They were injected with gentamicin sulfate (100 mg kg(-1) per day i.p.) and manganese chloride (2 or 20 mg kg(-1) per day i.p....
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043-6618(03)00227-5
更新日期：2003-12-01 00:00:00
abstract：AIM:Acute myocardial infarction and subsequent post-infarction heart failure are among the leading causes of mortality worldwide. The endocannabinoid system has emerged as an important modulator of cardiovascular disease, however the role of endocannabinoid metabolic enzymes in heart failure is still elusive. Herein, w...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2019.104578
更新日期：2020-01-01 00:00:00
abstract：:In recent decades, extracellular vesicles (EVs) have been proven to establish an important bridge of communication between cells or cells and their microenvironment. It is well known that EVs play crucial roles in many human diseases, especially in tumors. Tumor-derived EVs (TEVs) are not only involved in epithelial-m...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2020.105041
更新日期：2020-09-01 00:00:00
abstract：:Inflammation plays a key role in tumor promotion and development. Indeed, cyclooxygenase-2 (COX-2) expression is strongly associated with different types of cancer. An emerging class of compounds with significant anti-inflammatory properties is the hydrogen sulfide-releasing non-steroidal anti-inflammatory drugs (H2S-...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2016.10.019
更新日期：2016-12-01 00:00:00
abstract：:Oxidative stress is an important contributor to the risk of chronic diseases. Dietary guidelines recommend increased consumption of fruits and vegetables to combat the incidence of human diseases such as cancer, cardiovascular disease, osteoporosis and diabetes. Fruits and vegetables are good sources of antioxidant ph...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2007.01.012
更新日期：2007-03-01 00:00:00
abstract：:Many data suggest an involvement of toxic oxygen radicals in the termination of endurance to muscle fatigue. Being reduced glutathione (GSH), an efficient intracellular physiological antioxidant, experiments have been performed to discover whether exogenous GSH modifies endurance to exhaustive swimming in mice. GSH wa...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043-6618(05)80116-1
更新日期：1991-02-01 00:00:00
abstract：:The hepatoprotective effects of acetylbergenin were examined against D -galactosamine (GalN)-induced liver damage in rats, compared with that of bergenin reported previously. Acetylbergenin was synthesized from acetylation of bergenin, isolated from Mallotus japonicus, to increase lipophilic and physiological activiti...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.2000.0730
更新日期：2000-11-01 00:00:00
abstract：:Cytochrome P450-dependent arachidonic acid (AA) metabolism by medullary thick ascending limb of the loop of Henle (mTALH) cells, corneal epithelium and other transporting epithelia, such as those of the intestines, generate metabolites which affect Na(+)-K(+)-ATPase activity, vasomotion and, thereby, organ function. F...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/1043-6618(91)90046-z
更新日期：1991-05-01 00:00:00
abstract：:The pharmacokinetics of single intravenous and intramuscular administrations and milk antimicrobial equivalent activity of enrofloxacin at a dose of 5 mg per kilogram body weight were studied in clinically healthy lactating goats which were either not treated or had received 7.5 mg per kilogram body weight of albendaz...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043-6618(03)00179-8
更新日期：2003-10-01 00:00:00
abstract：:Secretion of matrix metalloproteinases (MMPs) by macrophages and smooth muscle cells (SMC) may impair atherosclerotic cap integrity leading to atherosclerosis complications. Selective estrogen receptor modulators (SERMs) have favourable impact on plasma lipid levels, but their role in the prevention of atherosclerosis...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2007.05.004
更新日期：2007-08-01 00:00:00
abstract：:Augmented vasoconstriction is a hallmark of hypertension and is mediated partly by hyper-stimulation of G protein couple receptors (GPCRs) and downstream signaling components. Although GPCR blockade is a key component of current anti-hypertensive strategies, whether hypertension is better managed by directly targeting...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2019.01.012
更新日期：2019-03-01 00:00:00
abstract：:The role of autophagy, a process in which the cell self-digests its own components, was investigated in glioma cell death induced by the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase-inhibiting drug simvastatin. Induction of autophagy and activation of autophagy-regulating signalling pathways were analyzed by i...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2011.08.003
更新日期：2012-01-01 00:00:00
abstract：:Dyslipidemia and hyperglycemia are associated with an increased risk of ischemic cardiovascular disease. Positive effects of a nutraceutical combination comprising red yeast rice, berberine, policosanol, astaxanthin, coenzyme Q10 and folic acid (NComb) on plasma lipid and glucose levels have been reported in some but ...
journal_title：Pharmacological research
pub_type： 杂志文章,meta分析,评审
doi：10.1016/j.phrs.2016.04.021
更新日期：2016-08-01 00:00:00
abstract：:Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide that afflicts human health. With the in-depth study of the disease, its pathogenesis has gradually become clear. Although great breakthroughs have been made in the research of ALD, the research and development of drugs related to ALD has...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2019.104501
更新日期：2019-12-01 00:00:00
