Antiplatelet agents’-ticagrelol and eptifibatide-safety in experimental colitis in mice

Petrović, Stanko; Vasiljevska, Milijana; Obradović, Slobodan; Tarabar, Dino; Doder, Radoje; Majstorović, Ivana; Petrović, Marijana; Magić, Zvonko; Cikota, Bojana; Perišić, Nenad; Brcerevic, Irina; Manojlovic, Nebojsa; Rančić, Nemanja

doi:10.5152/tjg.2020.19454

Cited by 3 publications

(2 citation statements)

References 22 publications

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“…It was also reported that MNS could inhibit Syk kinase that could modulate the activity of the ASC-containing inflammasome in macrophages by regulating the formation of ASC specks ( Hara et al, 2013 ), which was consistent with our results. Interestingly, MNS’s inhibitory effects on Syk kinase could inhibit platelet aggregation, which was also consistent with some reports of many antiplatelet drugs having good anti-inflammatory effects ( Nannizzi-Alaimo et al, 2003 ; Friedman et al, 2009 ; Patil et al, 2010 ; Petrovic et al, 2020 ). For example, as the current traditional IBD therapeutic agent, sulfasalazine has been proven to have an anti-platelet aggregation effect ( Patel et al, 2012 ).…”

Section: Discussionsupporting

confidence: 90%

3,4-Methylenedioxy-β-Nitrostyrene Alleviates Dextran Sulfate Sodium–Induced Mouse Colitis by Inhibiting the NLRP3 Inflammasome

et al. 2022

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Inflammatory bowel disease (IBD) has been reported to be associated with NLRP3 inflammasome activation. Therefore inhibiting inflammasome activation could be a new approach to treat IBD. Inflammasome inhibitors NLRP3-IN-2, JC124, and 3,4-methylenedioxy-β-nitrostyrene (MNS) were previously reported to exert anti-inflammatory effects in various disease models but not in the dextran sulfate sodium (DSS)–induced colitis model. Here, we showed that MNS was more efficient in inhibiting the secretion of interleukin-1β (IL-1β) by blocking oligomerization of apoptosis-associated speck-like protein (ASC) than NLRP3-IN-2 and JC124. To investigate the protective effects of MNS on enteritis, we administered intragastric MNS to DSS-induced colitis mice. The results demonstrated that MNS attenuated DSS-induced body weight loss, colon length shortening, and pathological damage. In addition, MNS inhibited the infiltration of macrophages and inflammatory cells and reduced IL-1β and IL-12p40 pro-inflammatory cytokines but had no significant effect on tumor necrosis factor α (TNF-α) and IL-6. Furthermore, we also found that the differentiation of IL-17A+interferon-γ (IFN-γ)+CD4+ T cell was decreased in the colon after MNS treatment, which might be mediated by IL-1β, etc. cytokine release. Taken together, MNS alleviated DSS-induced intestinal inflammation by inhibiting NLRP3 inflammasome activation, which may function as an effective therapeutic for IBD.

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Section: Discussionsupporting

confidence: 90%

3,4-Methylenedioxy-β-Nitrostyrene Alleviates Dextran Sulfate Sodium–Induced Mouse Colitis by Inhibiting the NLRP3 Inflammasome

et al. 2022

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“…Mice were observed for stool consistency and rectal bleeding on a daily basis so that disease activity index (DAI) could be calculated daily as the sum of the weight loss score, the diarrheal score, and the hematochezia score based on the method used by Friedman et al, as shown in Table 1. The DAI was used to assess the severity of colitis [48].…”

Section: Antiplatelet Agents'-ticagrelor and Eptifibatide-safety In E...mentioning

confidence: 99%

Platelets in Ulcerative Colitis: From Pathophysiology to Therapy

Petrović¹,

Obradović²,

Petrović³

et al. 2022

Ulcerative Colitis - Etiology, Diagnosis, Diet, Special Populations, and the Role of Interventional Endoscopy

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Based on the role of platelets in inflammation and hemostasis it has been assumed that antiplatelet therapy could be beneficial for patients suffering from ulcerative colitis. Platelets present a link between inflammation and coagulation. They have more than 300 active mediators stored in their granules. Upon activation, platelet degranulate and release a lot of microparticles and mediators and interact with other immune and non-immune cells thereby amplifying inflammation. The most important parameters of platelet activation are P-selectin and CD40 ligand expressed on their surface upon activation, and their soluble forms presented in blood. Today, we have potent anti-platelet drugs that can inhibit platelet activation and degranulation, and thereby reduce inflammation. The most important drugs are P2Y12 receptor antagonists such as ticagrelor and clopidogrel and glycoprotein IIbIIIa inhibitors. Ticagrelor is an active drug and besides antiplatelet activity, it has bactericidal activity against Gram-positive strains and Clostridium difficile. Clopidogrel is a prodrug with less anti-inflammatory effect than ticagrelor and no proven bactericidal activity. Glycoprotein IIbIIIa inhibitors are very potent in reducing platelet aggregation but have lower anti-inflammatory potential than ticagrelor and clopidogrel.

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IL-1 and CD40/CD40L platelet complex: elements of induction of Crohn’s disease and new therapeutic targets

et al. 2021

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Antiplatelet agents’-ticagrelol and eptifibatide-safety in experimental colitis in mice

Cited by 3 publications

References 22 publications

3,4-Methylenedioxy-β-Nitrostyrene Alleviates Dextran Sulfate Sodium–Induced Mouse Colitis by Inhibiting the NLRP3 Inflammasome

3,4-Methylenedioxy-β-Nitrostyrene Alleviates Dextran Sulfate Sodium–Induced Mouse Colitis by Inhibiting the NLRP3 Inflammasome

Platelets in Ulcerative Colitis: From Pathophysiology to Therapy

IL-1 and CD40/CD40L platelet complex: elements of induction of Crohn’s disease and new therapeutic targets

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