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Acetyl salicylic acid resistance and inhibition to platelet aggregation
Published in Cut Adeya Adella, Stem Cell Oncology, 2018
D.M. Amoryna, Z. Mukthar, H. Hariman
Platelet aggregation is performed to identify and quantify platelet response and monitor platelet inhibition by drug therapy. It is based on the addition of a platelet agonist to a blood sample (usually platelet-rich plasma). It may be assessed using various agonists such as adenosine di-phosphate (ADP), collagen and others. Arachidonic acid (AA), a precursor of thromboxane A2 and hydroxyl fatty acids liberated from human platelets on activation, converts the enzyme cyclooxygenase-1 (COX-1) into a potent inducer of platelet aggregation. Ingestion of ASA inhibits COX-1 thus inhibits platelet aggregation. The aggregation of platelets is an essential physiologic life-saving process of blood coagulation. The role of platelets in haemostasis involves adherence to sites of injury, activation of internal signalling pathways, aggregation to form plugs and the acceleration of the coagulation reactions to form thrombin. Platelet aggregation, particularly at the site of plaque rupture, results in thrombus formation blocking normal blood circulation in the heart musculature in ACS (Fuster et al., 1996). Platelet function may be impaired if any of the pathways mediated by the activation process by agonists are defective. The objective of this small cohort study is to determine whether an ASA of 50 mg dose is as effective as a 100 mg dose in normal healthy subjects.
Drug-induced bronchospasm
Published in Philippe Camus, Edward C Rosenow, Drug-induced and Iatrogenic Respiratory Disease, 2010
K Suresh Babu, Jaymin Morjaria
It is recognized that there are at least two COX enzymes: COX-1 and COX-2. COX 1 and 2 are coded by two different genes. Recently COX-3 and two smaller forms of COX-1 – derived from COX-1 by alternative splicing of COX-1 mRNA – have been identified.110 COX-1 is the housekeeping enzyme (i.e. expressed in cells at baseline) while COX-2 is induced during inflammation and mainly enhances synthesis of inflammatory prostanoids. Bronchial biopsy studies show no difference in expression of COX-1 or COX-2 between subjects with AIA and non-AIA.111 In patients with AIA, the COX enzymes are very sensitive to ASA/NSAIDs, and studies have shown that inhibition of COX-1 but not COX-2 is responsible for precipitating bronchospasm.112,113 PGE2 is a key mediator in aspirin-induced asthma. PGE2 is pro-inflammatory in sepsis and arthritis but blunts and protects against bronchoconstriction following aspirin challenge. The levels of PGE2 and thromboxane B2 were decreased in patients with AIA and in the aspirin-tolerant asthma (ATA) groups.114
Analgesic, Anti-Inflammatory, Antipyretic, and Anesthetic Drugs: Dealing With Pain, Inflammation, and Fever
Published in Richard J. Sundberg, The Chemical Century, 2017
But no one knew how aspirin worked until the early 1970s, when John Vane and collaborators showed that it inhibited formation of prostaglandins.2 Vane shared the 1982 Nobel Prize in Medicine for this discovery.a The first enzyme in the biosynthetic pathway to prostaglandins is cyclooxygenase-1 (COX-1), so aspirin and related drugs became known as COX-1 inhibitors. The prostaglandins are biosynthesized from arachidonic acid, a highly unsaturated 20-carbon fatty acid. The cyclooxygenase enzyme contains a heme group that functions to form peroxides and hydroperoxides and a second site that converts these to hydroxyl and carbonyl groups.3 The two sites are linked by electron transfer. The key intermediate is prostaglandin endoperoxide (shown as PGH2 in Fig. 13.1), which gives rise to the prostaglandins and two related types of compounds, the thromboxanes and prostacyclin. As a group, these compounds are called eicosanoids, referring to their 20-carbon structures. Several of the prostaglandins are vasodilators and also effect blood clotting. The thromboxanes tend to be prothrombotic, vasoconstrictors and promote platelet aggregation. Prostacyclin (also called PGI2) has the opposite effects, acting as a vasodilator and inhibiting platelet aggregation. The balance between these effects is a critical aspect of their biological function. The eicosanoids are involved in several other important biological processes including, kidney function, asthma, maintenance of gastrointestinal mucosa, induction of sleep, and aspects of reproduction.
Review: Schiff base metal complexes as anti-inflammatory agents
Published in Journal of Coordination Chemistry, 2023
Qurat-Ul-Ain Sandhu, Muhammad Pervaiz, Abdul Majid, Umer Younas, Zohaib Saeed, Adnan Ashraf, Rana Rashad Mahmood Khan, Sami Ullah, Faisal Ali, Seemal Jelani
Most anti-inflammatory drugs are extracted from plant sources to get relief from pain and fever. Non-steroidal anti-inflammatory drugs (NSAIDs) are used as anti-inflammatory drugs. NSAIDs are generally composed of organic acids and later non-acidic compounds. Some anti-inflammatory drugs show less gastrointestinal side effects as compared to predecessors like aspirin and indomethacin [77]. The main function of NSAIDs is to block the COX enzyme and suppress the activity of prostaglandin. Two types of COX enzymes are known, COX-1 provides protection in gastrointestinal tract while COX-2 performs inflammatory signal activity [78].
Cu(II) complexes of hydrazones–NSAID conjugates: synthesis, characterization and anticancer activity
Published in Journal of Coordination Chemistry, 2020
Jatinder Kaur, Tanmayee Chikate, Parbati Bandyopadhyay, Soumya Basu, Rajeev Chikate
Nonsteroidal anti-inflammatory drugs (NSAIDs) consist of analgesic, antithrombotic antipyretic and anti-inflammatory agents that are commonly employed for the treatment of arthritis, spondylitis and ocular conditions for several decades [1–3]. The anti-inflammatory activity of NSAIDs is attributed to its irreversible inhibition of cyclo-oxygenase enzymes like COX-1 and COX-2 [4,5]. COX-1 is primarily responsible for “housekeeping” functions of tissues while COX-2 is expressed as a response towards tissue injuries for catalyzing the conversion of arachidonic acid to prostaglandins and thromboxane that are responsible for inflammation and mitogenesis of tissues and cells [6,7]. Interestingly, several epidemiologic and clinical investigations have suggested the chemopreventive and cytotoxic potency of NSAIDs against different types of cancers like colon, breast, lung, gastric and prostate [8–15]. Diclofenac, a nonsteroidal anti-inflammatory drug, exhibits enhanced ROS production and lowers the mitochondrial superoxide dismutase levels to exert cytotoxicity on human melanoma cell line A2058 [16]. Another compound of this class, ibuprofen, when administered in combination with cisplatin, improved the suppression of overexpressed Hsp70 protein in lung cancer cell line that triggers the mitochondrial apoptosis [17]. On the other hand, aspirin; an anti-pyretic and anti-inflammatory drug, suppresses the propagation of cervical cancer cell (HeLa) and induces apoptosis through inhibition of proto-oncogene (ErbB2) signaling pathway [18]. Thus, cytotoxic behavior of NSAIDs is attributed to a variety of mechanistical processes such as inhibition of COX-2 enzyme, inhibition of angiogenesis, disrupting glucose metabolism, blocking signal transduction pathways and triggered apoptosis [19–26].
Ingestion of Sudan IV-adulterated palm oil impairs hepato-renal functions and induces the overexpression of pro-inflammatory cytokines: A sub-acute murine model
Published in Egyptian Journal of Basic and Applied Sciences, 2022
Ofem E. Eteng, Ceaser A. Moses, Emmanuel I. Ugwor, Joe E. Enobong, Adio J. Akamo, Yewande Adebekun, Arikpo Iwara, Eyong Ubana
Inflammation, a component of the body’s intricate response to deleterious stimuli, such as xenobiotics and pathogens, is a defensive response involving several molecular mediators and the immune cells that secrete these mediators [30]. Mediators involved in the inflammatory process include the interleukins, TNF-α, CRP, and cyclooxygenases [30]. This study appraised the inflammatory response in the liver and kidneys following exposure to S4D-adulterated PO. In the liver, the expression of CRP and COX-2 were significantly elevated in the S4D-exposed groups. CRP is an acute-phase protein secreted predominantly by hepatocytes. CRP then binds to lysophosphatidylcholine present on the surface of dead or dying cells, thereby stimulating the immune system. Thus, the hepatic expression and therefore circulating levels of CRP are elevated during the inflammatory response [31]. Cyclooxygenases are enzymes concerned with the metabolism of arachidonic acid and biosynthesis of prostanoids, which are potent pro-inflammatory compounds [30]. While COX-1 is constitutively expressed in several tissues, the expression of COX-2 is inducible and becomes elevated during inflammation [32]. The elevated expression levels of CRP and COX-2, observed in this study, suggest that S4D dye invoked inflammation, in line with the study of [33]. This study reported that azo food dyes (sunset yellow, tartrazine, Allura red, and carmoisine) elicited cellular inflammatory responses and present potential health risks to the local population. On the other hand, liver expression of IL-10 was significantly repressed. IL-10 is an anti-inflammatory cytokine that predominantly inhibits the production of pro-inflammatory cytokines (e.g. TNFα and IL-1β) [34]. Thus, its repression further substantiates the postulated pro-inflammatory events instigated by S4D. The expression of BAX was also inhibited in the liver tissues of S4D-exposed rats, possibly alluding to its carcinogenic properties [13,35] since BAX is involved in p53-mediated apoptosis of aberrant cells and is inhibited in most carcinomas [36]. Moreover, the expression of acute-phase protein – CRP – was significantly elevated in the PO alone group. We attribute this inflammatory response to the rich saturated fatty acid (SFA) contents of PO, which are known initiators of inflammation via the TLR4/NFκB pathways [37]. However, the expressions of other mediators were comparable to the control, while the anti-inflammatory cytokine IL-10 was elevated in the PO alone group. The latter may be a compensatory response to check the possible inflammatory response elicited by the SFA in PO. However, its expression was progressively repressed as the concentration of S4D increased, suggesting a repressed anti-inflammatory response in the hepatic cells, in alignment with the elevated expression of CRP and COX-2 (both inflammatory mediators).