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Aspirin is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is used to treat include Kawasaki disease, pericarditis, and rheumatic fever.
Aspirin is also used long-term to help prevent further heart attacks, ischaemic strokes, and blood clots in people at high risk. For pain or fever, effects typically begin within 30 minutes. Aspirin works similarly to other NSAIDs but also suppresses the normal functioning of platelets.
One common adverse effect is an upset stomach. More significant side effects include stomach ulcers, stomach bleeding, and worsening asthma. Bleeding risk is greater among those who are older, drink alcohol, take other NSAIDs, or are on other blood thinners. Aspirin is not recommended in the last part of pregnancy. It is not generally recommended in children with infections because of the risk of Reye syndrome. High doses may result in ringing in the ears.
A precursor to aspirin found in the bark of the willow tree (genus Salix) has been used for its health effects for at least 2,400 years. In 1853, chemist Charles Frédéric Gerhardt treated the medicine sodium salicylate with acetyl chloride to produce acetylsalicylic acid for the first time. Over the next 50 years, other chemists, mostly of the German company Bayer, established the chemical structure and devised more efficient production methods.: 69–75 Felix Hoffmann (or Arthur Eichengrün) of Bayer was the first to produce acetylsalicylic acid in a pure, stable form in 1897. By 1899, Bayer had dubbed this drug Aspirin and was selling it globally.: 27
Aspirin is available without medical prescription as a proprietary or generic medication in most jurisdictions. It is one of the most widely used medications globally, with an estimated 40,000 tonnes (44,000 tons) (50 to 120 billion pills) consumed each year, and is on the World Health Organization's List of Essential Medicines. In 2022, it was the 36th most commonly prescribed medication in the United States, with more than 16 million prescriptions. |
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InChI=1S/C9H8O4/c1-6(10)13-8-5-3-2-4-7(8)9(11)12/h2-5H,1H3,(H,11,12) |
BSYNRYMUTXBXSQ-UHFFFAOYSA-N |
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Bronsted acid
A molecular entity capable of donating a hydron to an acceptor (Bronsted base).
(via oxoacid )
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drug allergen
Any drug which causes the onset of an allergic reaction.
EC 1.1.1.188 (prostaglandin-F synthase) inhibitor
An EC 1.1.1.* (oxidoreductase acting on donor CH-OH group, NAD+ or NADP+ acceptor) inhibitor that interferes with the action of prostaglandin-F synthase (EC 1.1.1.188).
cyclooxygenase 2 inhibitor
A cyclooxygenase inhibitor that interferes with the action of cyclooxygenase 2.
cyclooxygenase 1 inhibitor
A cyclooxygenase inhibitor that interferes with the action of cyclooxygenase 1.
prostaglandin antagonist
A compound that inhibits the action of prostaglandins.
teratogenic agent
A role played by a chemical compound in biological systems with adverse consequences in embryo developments, leading to birth defects, embryo death or altered development, growth retardation and functional defect.
non-narcotic analgesic
A drug that has principally analgesic, antipyretic and anti-inflammatory actions. Non-narcotic analgesics do not bind to opioid receptors.
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plant activator
Any compound that protects plants by activating their defence mechanisms.
drug allergen
Any drug which causes the onset of an allergic reaction.
geroprotector
Any compound that supports healthy aging, slows the biological aging process, or extends lifespan.
platelet aggregation inhibitor
A drug or agent which antagonizes or impairs any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.
antipyretic
A drug that prevents or reduces fever by lowering the body temperature from a raised state. An antipyretic will not affect the normal body temperature if one does not have fever. Antipyretics cause the hypothalamus to override an interleukin-induced increase in temperature. The body will then work to lower the temperature and the result is a reduction in fever.
prostaglandin antagonist
A compound that inhibits the action of prostaglandins.
anticoagulant
An agent that prevents blood clotting.
non-steroidal anti-inflammatory drug
An anti-inflammatory drug that is not a steroid. In addition to anti-inflammatory actions, non-steroidal anti-inflammatory drugs have analgesic, antipyretic, and platelet-inhibitory actions. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins.
non-narcotic analgesic
A drug that has principally analgesic, antipyretic and anti-inflammatory actions. Non-narcotic analgesics do not bind to opioid receptors.
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View more via ChEBI Ontology
2-(acetyloxy)benzoic acid
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acide acétylsalicylique
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ChemIDplus
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ácido acetilsalicílico
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NIST Chemistry WebBook
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acidum acetylsalicylicum
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NIST Chemistry WebBook
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2-(ACETYLOXY)BENZOIC ACID
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PDBeChem
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2-Acetoxybenzenecarboxylic acid
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KEGG COMPOUND
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2-acetoxybenzoic acid
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ChemIDplus
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Acetylsalicylate
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KEGG COMPOUND
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Acetylsalicylic acid
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KEGG COMPOUND
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Acetylsalicylsäure
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ChemIDplus
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acide 2-(acétyloxy)benzoïque
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IUPAC
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ASA
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ChemIDplus
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Aspirin
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KEGG COMPOUND
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Azetylsalizylsäure
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ChEBI
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o-acetoxybenzoic acid
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NIST Chemistry WebBook
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O-acetylsalicylic acid
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ChemIDplus
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o-carboxyphenyl acetate
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NIST Chemistry WebBook
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salicylic acid acetate
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ChemIDplus
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74
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DrugCentral
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AIN
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PDBeChem
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Aspirin
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Wikipedia
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C01405
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KEGG COMPOUND
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CPD-524
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MetaCyc
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D00109
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KEGG DRUG
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DB00945
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DrugBank
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HMDB0001879
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HMDB
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LSM-5288
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LINCS
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View more database links |
218864
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Gmelin Registry Number
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Gmelin
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50-78-2
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CAS Registry Number
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NIST Chemistry WebBook
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50-78-2
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CAS Registry Number
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ChemIDplus
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779271
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Reaxys Registry Number
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Reaxys
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Ayyadevara S, Bharill P, Dandapat A, Hu C, Khaidakov M, Mitra S, Shmookler Reis RJ, Mehta JL (2013) Aspirin inhibits oxidant stress, reduces age-associated functional declines, and extends lifespan of Caenorhabditis elegans. Antioxidants & redox signaling 18, 481-490 [PubMed:22866967] [show Abstract]
AimsOxidative stress and inflammation are leading risk factors for age-associated functional declines. We assessed aspirin effects on endogenous oxidative-stress levels, lifespan, and age-related functional declines, in the nematode Caenorhabditis elegans.ResultsBoth aspirin and its salicylate moiety, at nontoxic concentrations (0.5-1 mM), attenuated endogenous levels of reactive oxygen species (p<0.001), and upregulated antioxidant genes encoding superoxide dismutases (especially sod-3, p<0.001), catalases (especially ctl-2, p<0.0001), and two glutathione-S-transferases (gst-4 and gst-10; each p<0.005). Aspirin, and to a lesser degree salicylate, improved survival of hydrogen peroxide, and in the absence of exogenous stress aspirin extended lifespan by 21%-23% (each p<10(-9)), while salicylate added 14% (p<10(-6)). Aspirin and salicylate delayed age-dependent declines in motility and pharyngeal pumping (each p<0.005), and decreased intracellular protein aggregation (p<0.0001)-all established markers of physiological aging-consistent with slowing of the aging process. Aspirin fails to improve stress resistance or lifespan in nematodes lacking DAF-16, implying that it acts through this FOXO transcription factor.InnovationStudies in mice and humans suggest that aspirin may protect against multiple age-associated diseases by reducing all-cause mortality. We now demonstrate that aspirin markedly slows many measures of aging in the nematode.ConclusionsAspirin treatment is associated with diminished endogenous oxidant stress and enhanced resistance to exogenous peroxide, both likely mediated by activation of antioxidant defenses. Our evidence indicates that aspirin attenuates insulin-like signaling, thus protecting against oxidative stress, postponing age-associated functional declines and extending C. elegans lifespan under benign conditions. | Lanas A, Wu P, Medin J, Mills EJ (2011) Low doses of acetylsalicylic acid increase risk of gastrointestinal bleeding in a meta-analysis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 9, 762-768.e6 [PubMed:21699808] [show Abstract]
Background & aimsWe performed a meta-analysis of data from randomized trials to estimate the risk of all-cause mortality and bleeding (and especially gastrointestinal [GI] bleeding) in patients treated with low doses of acetylsalicylic acid (ASA) (75-325 mg/d), alone or in combination with other medications.MethodsWe searched 10 electronic databases (until October 2010) and collected data on adverse events in randomized controlled studies that evaluated low doses of ASA, alone (35 trials) or in combination with anticoagulants (18 trials), clopidogrel (5 trials), or proton pump inhibitors (PPIs; 3 trials). We analyzed data using random-effects meta-analysis and meta-regression, applying Peto's odds ratio (OR) for adverse events.ResultsLow doses of ASA alone decreased the risk for all-cause mortality (relative risk, 0.93, 95% confidence interval [CI], 0.87-0.99), largely because of effects in secondary prevention populations. The risk of major GI bleeding increased with low doses of ASA alone (OR, 1.55; 95% CI, 1.27-1.90), compared with inert control reagents. The risk increased when ASA was combined with clopidogrel, compared with aspirin alone (OR, 1.86; 95% CI, 1.49-2.31), anticoagulants vs low doses of ASA alone (OR, 1.93; 95% CI, 1.42-2.61), or in studies that included patients with a history of GI bleeding or of longer duration. Importantly, PPI use reduced the risk for major GI bleeding in patients given low doses of ASA (OR, 0.34; 95% CI, 0.21-0.57).ConclusionsIn a meta-analysis, low doses of ASA increased the risk for GI bleeding; risk increased with accompanying use of clopidogrel and anticoagulant therapies, but decreased in patients who took PPIs. | Deng L, Hu S, Baydoun AR, Chen J, Chen X, Cong X (2009) Aspirin induces apoptosis in mesenchymal stem cells requiring Wnt/beta-catenin pathway. Cell proliferation 42, 721-730 [PubMed:19706045] [show Abstract]
Background and objectivesMesenchymal stem cells (MSC) are multipotent progenitor cells that are have found use in regenerative medicine. We have previously observed that aspirin, a widely used anti-inflammatory drug, inhibits MSC proliferation. Here we have aimed to elucidate whether aspirin induces MSC apoptosis and whether this is modulated through the Wnt/beta-catenin pathway.Materials and methodsApoptosis of MSCs was assessed using Hoechst 33342 dye and an Annexin V-FITC/PI Apoptosis Kit. Expression of protein and protein phosphorylation were investigated using Western blot analysis. Caspase-3 activity was detected by applying a caspase-3/CPP32 Colorimetric Assay Kit.ResultsIn these MSCs, aspirin induced morphological changes characteristic of apoptosis, cytochrome c release from mitochondria, and caspase-3 activation. Stimulating the Wnt/beta-catenin pathway by both Wnt 3a and GSK-3beta inhibitors (LiCl and SB 216763), blocked aspirin-induced apoptosis and protected mitochondrial function, as demonstrated by decreased cytochrome c release and caspase-3 activity. Aspirin initially caused a time-dependent decrease in COX-2 expression but subsequently, and unexpectedly, elevated the latter. Stimulation of COX-2 expression by aspirin was further enhanced following stimulation of the Wnt/beta-catenin pathway. Application of the COX-2 inhibitor NS-398 suppressed elevated COX-2 expression and promoted aspirin-induced apoptosis.ConclusionThese results demonstrate that the Wnt/beta-catenin pathway is a key modulator of aspirin-induced apoptosis in MSCs by regulation of mitochrondrial/caspase-3 function. More importantly, our findings suggest that aspirin may influence MSC survival under certain conditions; therefore, it should be used with caution when considering regenerative MSC transplantation in patients with concomitant chronic inflammatory diseases such as arthritis. | Byrns MC, Penning TM (2009) Type 5 17beta-hydroxysteroid dehydrogenase/prostaglandin F synthase (AKR1C3): role in breast cancer and inhibition by non-steroidal anti-inflammatory drug analogs. Chemico-biological interactions 178, 221-227 [PubMed:19010312] [show Abstract] Aldo-keto reductase (AKR) 1C3 catalyzes the NADPH-dependent reduction of Delta(4)-androstene-3,17-dione to yield testosterone, reduction of estrone to yield 17beta-estradiol and reduction of progesterone to yield 20alpha-hydroxyprogesterone. In addition, it functions as a prostaglandin (PG) F synthase and reduces PGH(2) to PGF(2)alpha and PGD(2) to 11beta-PGF(2). Immunohistochemistry showed that AKR1C3 is over-expressed in invasive ductal carcinoma of the breast. Retroviral expression of AKR1C3 in MCF-7 breast carcinoma cells shows that each of the assigned reactions occur in a breast cell microenvironment. Steroid and prostaglandin conversions were monitored by radiochromatography. Prostaglandin conversion was validated by a second method using HPLC coupled to APCI-MRM/MS. The combined effect of the AKR1C3 catalyzed 17- and 20-ketosteroid reductions will be to increase the 17beta-estradiol:progesterone ratio in the breast. In addition, formation of PGF(2) epimers would activate F prostanoid receptors and deprive PPARgamma of its putative anti-proliferative PGJ(2) ligands. Thus, AKR1C3 is a source of proliferative signals and a potential therapeutic target for hormone-dependent and -independent breast cancer. Two strategies for AKR1C3 inhibition based on non-steroidal anti-inflammatory drugs were developed. The first strategy uses the Ullmann coupling reaction to generate N-phenylanthranilate derivatives that inhibit AKR1C enzymes without affecting PGH(2) synthase (PGHS) 1 or PGHS-2. The second strategy exploits the selective inhibition of AKR1C3 by indomethacin, which did not inhibit highly related AKR1C1 or AKR1C2. Using known structure-activity relationships for the inhibition of PGHS-1 and PGHS-2 by indole acetic acids we obtained N-(4-chlorobenzoyl)-melatonin as a specific AKR1C3 inhibitor (K(I)=6.0muM) that does not inhibit PGHS-1, PGHS-2, AKR1C1, or AKR1C2. Both strategies are informed by crystal structures of ternary AKR1C3.NADP(+).NSAID complexes. The identification of NSAID analogs as specific inhibitors of AKR1C3 will help validate its role in the proliferation of breast cancer cells. | Anavekar NS, Murphy JG (2009) Aspirin and infective endocarditis: an ancient medicine used to fight an ancient disease-but does it work? The Journal of infection 58, 329-331 [PubMed:19386367] | Strong R, Miller RA, Astle CM, Floyd RA, Flurkey K, Hensley KL, Javors MA, Leeuwenburgh C, Nelson JF, Ongini E, Nadon NL, Warner HR, Harrison DE (2008) Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice. Aging cell 7, 641-650 [PubMed:18631321] [show Abstract] The National Institute on Aging's Interventions Testing Program was established to evaluate agents that are purported to increase lifespan and delay the appearance of age-related disease in genetically heterogeneous mice. Up to five compounds are added to the study each year and each compound is tested at three test sites (The Jackson Laboratory, University of Michigan, and University of Texas Health Science Center at San Antonio). Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen, 4-OH-alpha-phenyl-N-tert-butyl nitrone, or nordihydroguaiaretic acid (NDGA). Sample size was sufficient to detect a 10% difference in lifespan in either sex,with 80% power, using data from two of the three sites. Pooling data from all three sites, a log-rank test showed that both NDGA (p=0.0006) and aspirin (p=0.01) led to increased lifespan of male mice. Comparison of the proportion of live mice at the age of 90% mortality was used as a surrogate for measurement of maximum lifespan;neither NDGA (p=0.12) nor aspirin (p=0.16) had a significant effect in this test. Measures of blood levels of NDGA or aspirin and its salicylic acid metabolite suggest that the observed lack of effects of NDGA or aspirin on life span in females could be related to gender differences in drug disposition or metabolism. Further studies are warranted to find whether NDGA or aspirin, over a range of doses,might prove to postpone death and various age-related outcomes reproducibly in mice. | Watson HG, Chee YL (2008) Aspirin and other antiplatelet drugs in the prevention of venous thromboembolism. Blood reviews 22, 107-116 [PubMed:18226435] [show Abstract] While there is good evidence for a protective effect of aspirin against occlusive vascular events in individuals with arterial disease, its role in preventing venous thromboembolism (VTE) is unclear. In this article we review the role of aspirin and other antiplatelet drugs in prevention of venous thromboembolism in surgical patients, high risk medical patients requiring aspirin for other reasons, patients with myeloproliferative disorders, long distance travellers and patients receiving treatment with the IMiD class of drugs. Overall, data from the PEP study and Anti-Platelet Trialists' systematic review show that aspirin reduces the risk of VTE by around 25% in high risk surgical patients. Data from retrospective and before/after studies also suggest efficacy in reducing VTE in myeloma patients on IMiD drugs in combination with dexamethasone or chemotherapy. However, there has been no direct comparison with coumarins or heparin to indicate that aspirin is the optimal form of thromboprophylaxis. In patients who require aspirin because of high risk of arterial vascular occlusion (including patients with polycythaemia vera and essential thrombocythaemia), the additional small reduction in VTE risk is an added benefit with no additional risk associated. There is no evidence for a role of aspirin in prevention of travel-related thrombosis. At present there is no clear evidence that aspirin is the drug of choice for the prevention of VTE in any patient group. | García-Heredia JM, Hervás M, De la Rosa MA, Navarro JA (2008) Acetylsalicylic acid induces programmed cell death in Arabidopsis cell cultures. Planta 228, 89-97 [PubMed:18335236] [show Abstract] Acetylsalicylic acid (ASA), a derivative from the plant hormone salicylic acid (SA), is a commonly used drug that has a dual role in animal organisms as an anti-inflammatory and anticancer agent. It acts as an inhibitor of cyclooxygenases (COXs), which catalyze prostaglandins production. It is known that ASA serves as an apoptotic agent on cancer cells through the inhibition of the COX-2 enzyme. Here, we provide evidences that ASA also behaves as an agent inducing programmed cell death (PCD) in cell cultures of the model plant Arabidopsis thaliana, in a similar way than the well-established PCD-inducing agent H(2)O(2), although the induction of PCD by ASA requires much lower inducer concentrations. Moreover, ASA is herein shown to be a more efficient PCD-inducing agent than salicylic acid. ASA treatment of Arabidopsis cells induces typical PCD-linked morphological and biochemical changes, namely cell shrinkage, nuclear DNA degradation, loss of mitochondrial membrane potential, cytochrome c release from mitochondria and induction of caspase-like activity. However, the ASA effect can be partially reverted by jasmonic acid. Taking together, these results reveal the existence of common features in ASA-induced animal apoptosis and plant PCD, and also suggest that there are similarities between the pathways of synthesis and function of prostanoid-like lipid mediators in animal and plant organisms. | Huang ZW, Luo Y, Wu Z, Tao Z, Jones RO, Zhao HB (2005) Paradoxical enhancement of active cochlear mechanics in long-term administration of salicylate. Journal of neurophysiology 93, 2053-2061 [PubMed:15590729] [show Abstract] Aspirin (salicylate) is a common drug and frequently used long term in the clinic. It has been well documented that salicylate can cause reversible hearing loss and tinnitus and diminish outer hair cell (OHC) electromotility, which is capable of actively boosting the basilar membrane vibration and producing acoustic emission. However, aspirin's ototoxic mechanisms still remain largely unclear. In this experiment, the effects of long-term salicylate administration on cochlear hearing functions were investigated by measuring distortion product otoacoustic emissions (DPOAEs) in awake guinea pigs. A single injection of sodium salicylate (200 mg/kg) could reduce the amplitude of the cubic distortion product of 2f1-f2 within 2 h. The reduction was significant at 20-50 dB SPL stimulus levels and recovered after 8 h. However, following daily injections of sodium salicylate (200 mg/kg, b.i.d.), the distortion product of 2f1-f2 progressively increased. After injection for 14 days, the distortion product increased about 2-3.5 dB SPL. The increase rate was about 0.2 dB SPL/day. The DP-I/O function remained nonlinear. The increase was greater at 40-70 dB SPL primary sound intensities and reversible. After cessation of salicylate treatment for 4 wk, the increased distortion product returned to the initial normal levels. The rate of recovery was 0.1 dB SPL/day. In the control animals with saline injection, there was no change in DPOAEs. The data revealed that long-term administration of salicylate could paradoxically enhance active cochlear mechanics. The data also suggested that salicylate-induced tinnitus might be generated at the OHC level. | Witte KK, Clark AL (2004) The effect of aspirin on the ventilatory response to exercise in chronic heart failure. European journal of heart failure 6, 745-748 [PubMed:15542410] [show Abstract]
IntroductionPatients with chronic heart failure (CHF) experience breathlessness and fatigue on exercise. One of the abnormalities seen on maximal exercise testing is an increased ventilatory response to exercise (VE/VCO(2) slope). The cause of this is unknown, but is likely to be due to a combination of interacting peripheral and central factors. Recent data have demonstrated a relation between VE/VCO(2) slope and prostaglandin levels in contracting muscles. The present study examined the influence of the presence of a potent non-selective prostaglandin inhibitor, aspirin, on the ventilatory response to exercise in a group of patients with CHF.MethodsWe investigated the ventilatory response to exercise of 120 consecutive patients in sinus rhythm attending a specialist heart failure clinic. We excluded those taking clopidogrel (six patients) and those on both warfarin and aspirin or taking other non-steroidal anti-inflammatory agents (five patients). The other 109 patients were grouped according to whether they were taking aspirin (n=52 (48%)) or not (n=57 (52%)). Each patient underwent echocardiography to assess left ventricular function, and exercise testing with metabolic gas exchange to derive peak oxygen consumption (pVO(2)) and the VE/VCO(2) slope.ResultsThe groups were similar in terms of age, (67 (13) vs. 66 (12) years; P=0.34) drug use, heart failure aetiology, left ventricular function (ejection fraction; 33.3 (9.4) vs. 31.8 (9.9)%; P=0.05)) and exercise tolerance (pVO(2); 20.4 (5.3) vs. 19.9 (6.0); P=0.68, and VE/VCO(2) slope; 35.4 (6.2) vs. 35.7 (9.3); P=0.73). There was no difference in the ventilatory response to exercise or the symptoms of breathlessness between the two groups.ConclusionsAspirin does not appear to affect exercise performance in CHF. | Streck RD, Kumpf SW, Ozolins TR, Stedman DB (2003) Rat embryos express transcripts for cyclooxygenase-1 and carbonic anhydrase-4, but not for cyclooxygenase-2, during organogenesis. Birth defects research. Part B, Developmental and reproductive toxicology 68, 57-69 [PubMed:12852484] [show Abstract]
BackgroundAcetylsalicylic acid (ASA) is a rat teratogen, and exposures on gestational days (GDs) 9 and 10 induce diaphragm, cardiac, and midline defects. ASA inhibits members of the cyclooxygenase (COX) family and potentially members of the carbonic anhydrase (CA) family. The objective of this study was to determine whether the mRNA developmental expression pattern for any COX or CA isoform was consistent with a model in which ASA teratogenicity is mediated through direct interaction with one of these enzymes within embryos or within the adjacent ectoplacental cone (EPC) or yolk sac.MethodsStaged embryos, over a range (GD 9.5-12) that included ASA-sensitive and ASA-insensitive stages of organogenesis, were assayed for COX and CA mRNA levels by three techniques: microarrays; in situ hybridization quantitated by a micro-imager; and quantitative reverse transcription polymerase chain reaction. ASA- and vehicle-treated embryos also were compared to determine whether inhibition led to upregulated COX or CA mRNA expression.ResultsCOX-2 mRNA was undetectable in embryos throughout organogenesis by any assay (although it was abundant in EPC). In contrast, COX-1 mRNA was moderately abundant in embryos throughout organogenesis. One CA isoform, CA-4, demonstrated developmentally regulated embryonic mRNA expression that coincided with ASA sensitivity ASA exposure failed to induce upregulation of any of these mRNAs.ConclusionsAlthough ASA may affect the embryo indirectly through interaction with COX-2 within EPC, failure to detect embryonic COX-2 mRNA argues against COX-2 functioning as a direct mediator of ASA teratogenic activity in induction of cardiac, diaphragm, and midline defects. Correlation of COX-1 and CA-4 expression with ASA sensitivity suggested that embryonic COX-1 and possibly CA4 are much more likely candidates for mediators of ASA developmental toxicity. | Kutuk O, Basaga H (2003) Aspirin prevents apoptosis and NF-kappaB activation induced by H2O2 in hela cells. Free radical research 37, 1267-1276 [PubMed:14753751] [show Abstract] The classical pathway of nuclear factor-kappa B (NF-kappaB) activation by several inducers mainly involves the phosphorylation of IkappaBalpha by a signalsome complex composed of IkappaBalpha kinases (IKKalpha and IKKbeta). However, in some cell types hydrogen peroxide (H2O2) has been shown to activate an alternative pathway that does not involve the classical signalsome activation process. In this study, we demonstrate that H2O2 induced NF-kappaB activation in HeLa cells through phosphorylation and degradation of IkappaB proteins as shown by immunblot analysis. Our studies reveal that a commonly used non-steroid anti-inflammatory drug, acetylsalicylic acid (aspirin) prevents H2O2-induced NF-kappaB activation in a dose-dependent manner through inhibition of phosphorylation and degradation of IkappaBalpha and IkappaBbeta. Differential staining and DNA fragmentation analysis also show that aspirin preloading of HeLa cells also prevents H2O2-induced apoptosis in a dose-dependent manner with maximum efficiency at 10 mM concentration. Additionally, aspirin effectively prevents caspase-3 and caspase-9 (cysteinyl aspartate-specific proteases) activation by H2O2. These results suggest that NF-kappaB activation is involved in H2O2-induced apoptosis and aspirin may inhibit both processes simultaneously. | Bazzi MD, Rabbani N, Duhaiman AS (2002) Inhibition of camel lens zeta-crystallin by aspirin and aspirin-like analgesics. The international journal of biochemistry & cell biology 34, 70-77 [PubMed:11733186] [show Abstract] Camel lens zeta-crystallin was reversibly inhibited to various degrees by aspirin (acetyl salicylic acid) and the aspirin-like analgesics: paracetamol (acetaminophen) and ibuprofen (2-(4-isobutyl phenyl)-propionic acid). Among these, aspirin was the most potent inhibitor, causing nearly complete inhibition in a dose-dependent, but time-independent manner. Analysis of inhibition kinetics revealed that aspirin was uncompetitive inhibitor (K(i) 0.64 mM) with respect to NADPH and non-competitive inhibitor (K(i) 1.6 mM) with respect to the substrate, 9,10-phenanthrenequinone (PQ). Multiple-inhibition analysis showed that aspirin and pyridoxal 5' phosphate (PAL-P), a lysine specific reagent, simultaneously bound to a critical lysine residue located towards the NADPH binding region. Consistent with this, NADPH was able to substantially protect zeta-crystallin against aspirin, whereas PQ did not provide any protection. The results suggested that an essential lysine residue was the locus of aspirin binding. The inhibition of zeta-crystallin by aspirin and aspirin-like analgesics was reversible thus eliminating acetylation as a mechanism for inhibition. Reversible binding of aspirin to this lysine may cause steric hindrance resulting in uncompetitive inhibition with respect to NADPH. | Sexton RC (2001) Aspirin in cardiovascular disease. Tennessee medicine : journal of the Tennessee Medical Association 94, 208-210 [PubMed:11402787] [show Abstract] The historic genesis of aspirin as a therapeutic agent is discussed. The use of aspirin as a primary and secondary chemo-preventive agent is reviewed. Those who introduced aspirin in the late 19th century would be surprised by the uses of aspirin today. It is anticipated that existing and further studies on the use of aspirin as a primary preventive agent will establish its utility and a more precise niche for it as a chemo-preventive agent. Reports indicate that it may be useful as a chemo-preventive agent in the prevention and possibly in the treatment of cancer of the colon and other malignancies. This plebeian drug, aspirin, has earned a position, some would say an egalitarian position, along with thrombolysis and primary coronary angioplasty in the emergency treatment of AMI. There are those who would add an intravenous beta blocker and an ACE inhibitor to this regimen. The laborious history of aspirin should again remind clinicians that they should continue to heed the admonition of Alexander Pope when he asserted, "Be not the first by whom the new is tried nor yet the last to lay the old aside." | Schröder A, Levin RM, Kogan BA, Longhurst PA (2001) Aspirin treatment improves bladder function after outlet obstruction in rabbits. Urology 58, 608-613 [PubMed:11597554] [show Abstract]
ObjectivesTo examine whether bladder smooth muscle dysfunction after outlet obstruction could be altered by treatment with aspirin. Long-term outlet obstruction causes contractile and metabolic dysfunction of the bladder in vivo and in vitro. The evidence is growing that a decrease in bladder perfusion is an important cause of this phenomenon. The platelet aggregation inhibitor, acetylsalicylic acid (aspirin), has been used to improve perfusion of the heart for decades.MethodsTen male New Zealand white rabbits were obstructed for 4 weeks. Five rabbits received no further treatment (Obs), and 5 rabbits received 2 mg/kg/day aspirin (Obs+aspirin), administered by an osmotic pump implanted subcutaneously 1 week before the surgical obstruction. The bleeding time was measured to confirm the effectiveness of the aspirin treatment. Three different control groups were created: sham-operated rabbits, unobstructed rabbits with pumps containing DMSO (vehicle), and unobstructed rabbits with pumps containing aspirin. The contractile responses of bladder strips to field stimulation, adenosine triphosphate, carbachol, and KCl were determined. A section of each detrusor tissue was fixed in formalin and used to determine the smooth muscle and collagen (connective tissue) volume fraction.ResultsNo differences were found in the bladder weights or responses to stimuli in the different control groups, which were therefore combined. Partial bladder outlet obstruction caused significant increases in the bladder weight of the obstructed animals (Obs+aspirin, 10.15 +/- 0.87 g; Obs, 10.17 +/- 0.88 g; and controls, 2.87 +/- 0.21 g). The aspirin treatment increased the bleeding time from 1.7 +/- 0.3 minutes to 3.3 +/- 0.1 minutes. The responses to field stimulation were significantly reduced in all of the obstructed rabbits. However, the responses of the bladder strips from the Obs rabbits to field stimulation were impaired to a significantly greater degree than were those from the Obs+aspirin rabbits. The response to 32-Hz stimulation was reduced by 86% in the Obs group but by only 64% in the Obs+aspirin group. The responses to carbachol were significantly reduced by 62% in the strips from the Obs rabbits, but the responses of the strips from the Obs+aspirin rabbits were similar to the responses of the strips from the controls. The responses to KCl and adenosine triphosphate were reduced, although they just failed to achieve statistical significance using Bonferroni's analysis. The ratio of smooth muscle and connective tissue shifted slightly toward smooth muscle after 4 weeks of obstruction, but no difference was found with or without aspirin treatment.ConclusionsLow-dose aspirin has a small but significant protective effect on the contractile dysfunction induced by bladder outlet obstruction in rabbits, although the increase in bladder mass was not altered. Bladders of the same weight showed improved responses to all forms of stimulation after pretreatment with aspirin. Already used by millions of patients with heart diseases, aspirin could be a useful protection against contractile dysfunction of the obstructed bladder. | Epelde F, Garca-Castrillo Riesgo L, Loma-Osorio A, Verdier J, Recuerda Martnez E (2000) [The use of acetylsalicylic acid in patients with ischemic cardiomyopathy cared for in Spanish emergency services (results of the EVICURE Study). Evaluacion del Manejo de la cardiopatia isquemica en los Servicios de Urgencias Hospitalarios of the Sociedad Espanola de Medicina de Urgencias y Emergencias (SEMES)]. Medicina clinica 115, 455-457 [PubMed:11203441] [show Abstract]
BackgroundAcetyl salicylic acid is a drug with demonstrated effectiveness in ischemic cardiomyopathy. The objective of our study was to know the use of this drug in the emergency services of Spain.Patients and methodThe EVICURE study analyzes the use of acetyl salicylic acid in 35 emergency services of Spanish hospitals.Results2,168 patients were studied. Of the 473 patients with stable angina, 9.2% received acetyl salicylic acid before going to the hospital and 90,7% at the arrival to the hospital, of 1,067 with unstable angina 13% received acetyl salicylic acid before the arrival to the hospital and 56% at the arrival to the hospital. Of 600 patients affected of myocardial infarction only 17% received acetyl salicylic acid before the arrival to the hospital and 59.8% received this drug in the emergency room.ConclusionsThe use of acetyl salicylic acid in patients affected of ischemic cardiopathy assisted in the emergency services of Spain is improperly low. | Varga JM, Kalchschmid G, Klein GF, Fritsch P (1991) Mechanism of allergic cross-reactions--I. Multispecific binding of ligands to a mouse monoclonal anti-DNP IgE antibody. Molecular immunology 28, 641-654 [PubMed:1650428] [show Abstract] A recently developed solid-phase binding assay was used to investigate the specificity of ligand binding to a mouse monoclonal anti-dinitrophenyl IgE [IgE(aDNP)]. All DNP-amino acids, that were tested, inhibited the binding of radio-labeled IgE(aDNP) to DNP covalently attached to polystyrene microtiter plates; however, the concentration for 50% inhibition varied within four orders of magnitude, DNP-L-serine being the most, DNP-proline the least potent inhibitor. In addition to DNP analogues a large number (2074) of drugs and other compounds were tested for their ability to compete with DNP for the binding site of IgE(aDNP). At the concentrations used for screening 59% of the compounds had no significant inhibition; 19% inhibited the binding of IgE(aDNP) more than 50%. Several families of compounds (tetracyclines, polymyxines, phenotiazines, salicylates and quinones) of effective competitors were found. Within these families change in the functional groups attached to the "family stem" had major effects on the affinity of ligand binding. The occurrence frequencies of interactions of ligands with IgE(aDNP) is in good agreement with a semi-empirical model for multispecific antibody-ligand interactions. | Warrington RJ, Tse KS (1979) Lymphocyte transformation studies in drug hypersensitivity. Canadian Medical Association journal 120, 1089-1094 [PubMed:445303] [show Abstract] In a group of patients with clinically diagnosed drug hypersensitivity the in vitro lymphocyte response to the suspected drug was assessed by the lymphocyte transformation test. The test gave positive results in all 15 patients with penicillin-induced immediate or accelerated allergic reactions and positive immediate skin-test reactivity to the major or the minor antigenic determinant of penicillin, or both, but in only 3 of the 12 patients with delayed-onset maculopapular rashes induced by penicillin, despite positive immediate reactivity to the skin-test reagents.Lymphocyte stimulation greater than five times the control level was demonstrated for five patients with penicillin-induced erythroderma, Stevens-Johnson syndrome or a serum-sickness-like illness, or with methicillin-induced interstitial nephritis, all of whom had negative reactions to the appropriate skin-test reagents. A low level of stimulation was seen in eight other skin-test-negative patients with possible allergic reactions induced by penicillins. However, in all subjects tested the stimulation was significantly greater than the mean for control subjects.For 9 of 11 patients with isoniazid-induced hepatitis or maculopapular rashes, but for only 8 of 31 patients with eruptions induced by a variety of drugs other than penicillins and isoniazid, significant stimulation occurred in the lymphocyte transformation test.It is concluded that the lymphocyte transformation test is useful in the detection of hypersensitivity to the penicillins (although in IgE-mediated reactions skin testing is clearly preferable) and isoniazid but is of limited value in the demonstration of hypersensitivity to other drugs. |
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