Abstract:
:The endogenous gasotransmitter hydrogen sulphide (H2S) is an important regulator of the cardiovascular system, particularly of myocardial function. Moreover, H2S exhibits cardioprotective activity against ischemia/reperfusion (I/R) or hypoxic injury, and is considered an important mediator of "ischemic preconditioning", through activation of mitochondrial potassium channels, reduction of oxidative stress, activation of the endogenous "anti-oxidant machinery" and limitation of inflammatory responses. Accordingly, H2S-donors, i.e. pro-drugs able to generate exogenous H2S, are viewed as promising therapeutic agents for a number of cardiovascular diseases. The novel H2S-donor 4-carboxy phenyl-isothiocyanate (4CPI), whose vasorelaxing effects were recently reported, was tested here in different experimental models of myocardial I/R. In Langendorff-perfused rat hearts subjected to I/R, 4CPI significantly improved the post-ischemic recovery of myocardial functional parameters and limited tissue injury. These effects were antagonized by 5-hydroxydecanoic acid (a blocker of mitoKATP channels). Moreover, 4CPI inhibited the formation of reactive oxygen species. We found the whole battery of H2S-producing enzymes to be present in myocardial tissue: cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (MPST). Notably, 4CPI down-regulated the post-ischemic expression of CSE. In Langendorff-perfused mouse hearts, 4CPI reduced the post-ischemic release of norepinephrine and the incidence of ventricular arrhythmias. In both rat and mouse hearts, 4CPI did not affect the degranulation of resident mast cells. In isolated rat cardiac mitochondria, 4CPI partially depolarized the mitochondrial membrane potential; this effect was antagonized by ATP (i.e., the physiological inhibitor of KATP channels). Moreover, 4CPI abrogated calcium uptake in the mitochondrial matrix. Finally, in an in vivo model of acute myocardial infarction in rats, 4CPI significantly decreased I/R-induced tissue injury. In conclusion, H2S-donors, and in particular isothiocyanate-based H2S-releasing drugs like 4CPI, can actually be considered a suitable pharmacological option in anti-ischemic therapy.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Testai L,Marino A,Piano I,Brancaleone V,Tomita K,Di Cesare Mannelli L,Martelli A,Citi V,Breschi MC,Levi R,Gargini C,Bucci M,Cirino G,Ghelardini C,Calderone Vdoi
10.1016/j.phrs.2016.09.006subject
Has Abstractpub_date
2016-11-01 00:00:00pages
290-299issue
Pt Aeissn
1043-6618issn
1096-1186pii
S1043-6618(16)30523-0journal_volume
113pub_type
杂志文章abstract::As one classic anticancer drug, clinical application of Doxorubicin (Dox) is limited due to its side effects. In our previous work, we have investigated the drug targets to treat Dox-induced cardiotoxicity, hepatotoxicity and nephrotoxicity. In this paper, the mechanisms and new drug-target associated with Dox-induced...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2019.104276
更新日期:2019-08-01 00:00:00
abstract::The isolated heart is deservedly one of the most popular experimental models in cardiovascular research, both in terms of cost and the quality and quantity of data it provides. However, it is a deceptively simple model, capable of throwing many problems in the path of the inexperienced or unwary perfuser. The followin...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1006/phrs.1999.0653
更新日期:2000-06-01 00:00:00
abstract::Conjugated linoleic acid (CLA) is being sold as a panacea that has the capability of reducing or eliminating cancer, preventing heart disease, improving immune function, and altering body composition to treat obesity or build lean body mass. Unfortunately, there has been very little published human research on CLA. Th...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1006/phrs.2000.0735
更新日期:2000-12-01 00:00:00
abstract::Proton pump inhibitors (PPIs) are used widely for the treatment of acid-related disorders. Despite their excellent efficacy and tolerance, the pharmacodynamics and pharmacokinetics of PPIs are affected by each patient's CYP2C19 and gastric H+,K+-ATPase genotype. The aim of this review was to analyze the effect of gene...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2019.104606
更新日期:2020-02-01 00:00:00
abstract::We aimed to investigate the cardiac changes in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with trastuzumab in an adjuvant setting. Two hundred and fifty-three women with HER2-positive breast cancer were included. The assessment of cardiovascular system and echocardiogr...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2013.10.001
更新日期:2013-12-01 00:00:00
abstract::Cancer immunotherapy has come of age with the advent of immune checkpoint inhibitors. In this article we review how agonists for receptors of the innate immune system, the Toll-like receptors and the RIG-I-like receptors, impact anticancer immune responses. Treatment with these agonists enhances the activity of antica...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2019.03.001
更新日期:2020-04-01 00:00:00
abstract::Adaptive responses to stress are critical to enhance physical and mental well-being, but excessive or prolonged stress may cause inadaptability and increase the risks of psychiatric disorders, such as depression. GABABR signaling is fundamental to brain function and has been identified in neuropsychiatric disorders. K...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2020.105355
更新日期:2021-01-01 00:00:00
abstract::Heparin-binding protein (HBP; CAP37/azurocidin) is secreted from neutrophil leukocytes early during inflammation and plays a central role in early capillary leakage and extravasation of neutrophils. Furthermore, HBP is chemotactic towards monocytes and lymphocytes and protects against stress-induced apoptosis, e.g. in...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2005.01.004
更新日期:2005-06-01 00:00:00
abstract::The cytoprotective activity of alpha-lipoic acid against free radical toxicity, manifested during experimental hyperoxaluria, has been investigated. Glycollate was used as the inducer of oxalate hyperoxaluria in rats. The increase in lipid peroxidation and superoxide dismutase (SOD) activity, associated with a decreas...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1993.1031
更新日期:1993-05-01 00:00:00
abstract::Skeletal muscle fitness is vital for human health and disease and is determined by the capacity for burning fuel, mitochondrial ATP production, and contraction. High quality mitochondria in skeletal muscle are essential for maintaining energy homeostasis in response to a myriad of physiologic or pathophysiological str...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2018.12.020
更新日期:2019-03-01 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::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::Some macrolide antibiotics have been shown to produce significant drug-drug interactions through the inhibition of cytochrome P450 (CYP) enzymes. In renal transplant patients these interactions pose potentially serious problems for the safe administration of cyclosporine A (CSA), a substrate of CYP3A4. The effects of ...
journal_title:Pharmacological research
pub_type: 临床试验,杂志文章
doi:10.1016/s1043-6618(03)00018-5
更新日期:2003-06-01 00:00:00
abstract::Antifertility activity of a triterpenoid glycoside, DSS, isolated from the root of Dalbergia saxatilis was investigated in female Wistar rats of breeding age. When administered by gastric intubation at a dose rate of 200 mg kg(-1)body weight at the premating period, conception was inhibited in 71.4% of the treated ani...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1999.0615
更新日期:2000-05-01 00:00:00
abstract::Possible interaction between adenosine and L type Ca2+ channel in the locomotor activity of rats was investigated. R-PIA (0.05 mg kg-1), an adenosine analogue, and caffeine (20 mg kg-1), an adenosine receptor antagonist, significantly decreased and increased locomotor activity, respectively. Ca2+ channel blocker nifed...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1996.0021
更新日期:1996-02-01 00:00:00
abstract::Pharmacokinetics is a relatively young branch of the life sciences, which has developed rapidly in the last 15-20 years, thanks to a series of analytical achievements that have allowed drug concentrations to be measured in biological matrices with highly selective and sensitive methods. Most old drugs and all new drug...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1006/phrs.1997.0254
更新日期:1997-12-01 00:00:00
abstract::The DNA microarrays have proven to be a state of the art technique for high throughput comprehensive analysis of thousand of genes in parallel. The application of a DNA microarray to compare normal and pathological cells, tissues or organs may allow, along with classical positional cloning techniques, to speed up the ...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2003.06.001
更新日期:2004-04-01 00:00:00
abstract::Postnatal bone marrow contains a subtype of unique progenitor cells that have the capacity to differentiate into functional endothelial cells. Hence, these cells have been termed endothelial progenitor cells (EPCs). In general, circulating EPCs were characterized by the expression of CD133, CD34 and the vascular endot...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2008.07.008
更新日期:2008-08-01 00:00:00
abstract::As the capacity of the endogenous antioxidative system is limited, pharmacological treatment with antioxidants may help to protect neuronal tissue against increased amount of reactive oxygen species produced during oxidative stress. We attempted to improve resistance of rat hippocampal slices exposed to ischaemia in v...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2005.08.004
更新日期:2006-01-01 00:00:00
abstract::Sphingosine 1-phosphate (S1P) is an extracellular lipid signaling molecule that acts as a selective, high-affinity ligand for a family of five G protein-coupled receptors. This signaling system was first identified twenty years ago, and has since been shown to regulate a diverse range of physiological processes and di...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2016.09.025
更新日期:2016-11-01 00:00:00
abstract::Inflammatory reaction and cell apoptosis are two important processes in intestinal ischemia/reperfusion (II/R) injury, and exploration of effective lead compounds against II/R injury via regulating inflammation and apoptosis is critical important. In this paper, the results indicated that dioscin significantly increas...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2018.11.040
更新日期:2019-01-01 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::Evodiae fructus is a widely used herbal drug in traditional Chinese medicine. Evodia extract was found to inhibit hERG channels. The aim of the current study was to identify hERG inhibitors in Evodia extract and to investigate their potential proarrhythmic effects. Dehydroevodiamine (DHE) and hortiamine were identifie...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2018.02.024
更新日期:2018-05-01 00:00:00
abstract::Nephrotoxicity associated with cyclosporine A (CsA) administration is characterized by marked renal vasoconstriction, interstitial fibrosis and arteriolar hypertrophy. The molecular mechanisms of CsA nephrotoxicity are not well characterized, but previous studies have demonstrated that angiotensin II (Ang II), the pri...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.2002.0959
更新日期:2002-05-01 00:00:00
abstract::Prader-Willi syndrome (PWS), the leading genetic cause of obesity, is characterized by a striking hyperphagic behavior that can lead to obesity, type-2 diabetes, cardiovascular disease and death. The molecular mechanism underlying impaired satiety in PWS is unknown. Oleoylethanolamide (OEA) is a lipid mediator involve...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2016.12.024
更新日期:2017-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) hydrolyze endogenous cannabinoids (eCBs), N-arachidonoyl ethanolamine (AEA) and 2-arachidonoyl glycerol (2-AG), respectively. These enzymes also metabolize eCB analogs such as lipoamines and 2-acyl glycerols, most of...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2016.04.020
更新日期:2016-08-01 00:00:00
abstract::With more than four decades of clinical research and 25 years of clinical trials, much is known about the natural history of T1D before and after clinical diagnosis. We know that autoimmunity occurs early in life, that islet autoimmunity inevitably leads to clinically overt disease, and that some immune therapies can ...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2015.02.002
更新日期:2015-08-01 00:00:00
abstract::Cosmetics are largely diffused substances topically applied to wash, to perfume or to improve the look, nevertheless the number of reported adverse reactions is very low, probably because of underreporting. This could be due to self-diagnosis and self-medication that is common in the presence of not severe reactions. ...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2005.08.003
更新日期:2006-01-01 00:00:00
abstract::Cinnamaldehyde, one of the active components derived from Cinnamon, has been used as a natural flavorant and fragrance agent in kitchen and industry. Emerging studies have been performed over the past decades to evaluate its beneficial role in management of diabetes and its complications. This review highlights recent...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2017.05.019
更新日期:2017-08-01 00:00:00
abstract::The concentration of five lipid-soluble antioxidants (gamma- and alpha-tocopherol, lycopene, beta-carotene and ubiquinol-10) was measured in plasma and very low-density, low-density and high-density lipoproteins (VLDL, LDL and HDL) isolated from young healthy normo- cholesterolemic subjects. Alpha-tocopherol was the e...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1999.0552
更新日期:2000-01-01 00:00:00