Licofelone, a dual cyclooxygenase/5-lipoxygenase inhibitor, reverses endotoxin-induced impaired atrial chronotropic responsiveness to cholinergic stimulation in rats
Evidence show that endotoxemia is linked with tachycardia. The exact mechanism of tachycardia is not well-understood, but it seems that impaired cardiac chronotropic responsiveness to cholinergic stimulation plays a role in this phenomenon. The aim of this experiment was to study the effect of licof...
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| Veröffentlicht in: | European journal of pharmacology 2020-11, Vol.887, p.173569-173569, Article 173569 |
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| container_title | European journal of pharmacology |
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| creator | Nikoui, Vahid Mehrzadi, Saeed Khan, Muhammad Imran Aman, Waqar Ostadhadi, Sattar Dehpour, Ahmad Reza |
| description | Evidence show that endotoxemia is linked with tachycardia. The exact mechanism of tachycardia is not well-understood, but it seems that impaired cardiac chronotropic responsiveness to cholinergic stimulation plays a role in this phenomenon. The aim of this experiment was to study the effect of licofelone as a dual cyclooxygenase (COX)/5-lipoxygenase (5-LOX) inhibitor in modulation of atrial chronotropic hyporesponsiveness to cholinergic stimulation in endotoxemic rats, compared with hydrocortisone and indomethacin in in vitro and in vivo studies. Rats were injected by either of lipopolysaccharide (LPS) or saline. The isolated atria were incubated with licofelone, hydrocortisone, or indomethacin in an organ bath set up. In a separate experiment, rats were injected with licofelone, hydrocortisone, or indomethacin prior to isolation of the atria. Then, in both experiments, chronotropic responsiveness to cumulative concentrations of carbacholine in organ bath was recorded. LPS injection decreased the chronotropic responsiveness to cholinergic stimulation in both in vitro and in vivo experiments, significantly (P |
| doi_str_mv | 10.1016/j.ejphar.2020.173569 |
| format | Article |
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Our data revealed that in endotoxemic rats, chronotropic hyporesponsiveness to cholinergic stimulation was modulated by the dual COX/5-LOX inhibitor licofelone, and this effect is comparable with hydrocortisone and indomethacin.]]></description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2020.173569</identifier><identifier>PMID: 32949599</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Anti-Inflammatory Agents - pharmacology ; Arachidonate 5-Lipoxygenase - metabolism ; Carbachol - pharmacology ; Cholinergic Agents - pharmacology ; Chronotropic response ; Cyclooxygenase ; Cyclooxygenase Inhibitors - pharmacology ; Dose-Response Relationship, Drug ; Endotoxin ; Endotoxins ; Heart Atria - drug effects ; Heart Rate - drug effects ; Hydrocortisone - pharmacology ; Indomethacin - pharmacology ; Licofelone ; Lipopolysaccharides ; Lipoxygenase ; Lipoxygenase Inhibitors - pharmacology ; Male ; Parasympathetic Nervous System - drug effects ; Pyrroles - pharmacology ; Rats ; Rats, Wistar ; Systemic inflammation</subject><ispartof>European journal of pharmacology, 2020-11, Vol.887, p.173569-173569, Article 173569</ispartof><rights>2020 Elsevier B.V.</rights><rights>Copyright © 2020 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-f1685cee861814f165f35232c9c4b8b955a4a12031ef3dfec9ee8fe6e3b1ca7f3</citedby><cites>FETCH-LOGICAL-c362t-f1685cee861814f165f35232c9c4b8b955a4a12031ef3dfec9ee8fe6e3b1ca7f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejphar.2020.173569$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32949599$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nikoui, Vahid</creatorcontrib><creatorcontrib>Mehrzadi, Saeed</creatorcontrib><creatorcontrib>Khan, Muhammad Imran</creatorcontrib><creatorcontrib>Aman, Waqar</creatorcontrib><creatorcontrib>Ostadhadi, Sattar</creatorcontrib><creatorcontrib>Dehpour, Ahmad Reza</creatorcontrib><title>Licofelone, a dual cyclooxygenase/5-lipoxygenase inhibitor, reverses endotoxin-induced impaired atrial chronotropic responsiveness to cholinergic stimulation in rats</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description><![CDATA[Evidence show that endotoxemia is linked with tachycardia. The exact mechanism of tachycardia is not well-understood, but it seems that impaired cardiac chronotropic responsiveness to cholinergic stimulation plays a role in this phenomenon. The aim of this experiment was to study the effect of licofelone as a dual cyclooxygenase (COX)/5-lipoxygenase (5-LOX) inhibitor in modulation of atrial chronotropic hyporesponsiveness to cholinergic stimulation in endotoxemic rats, compared with hydrocortisone and indomethacin in in vitro and in vivo studies. Rats were injected by either of lipopolysaccharide (LPS) or saline. The isolated atria were incubated with licofelone, hydrocortisone, or indomethacin in an organ bath set up. In a separate experiment, rats were injected with licofelone, hydrocortisone, or indomethacin prior to isolation of the atria. Then, in both experiments, chronotropic responsiveness to cumulative concentrations of carbacholine in organ bath was recorded. LPS injection decreased the chronotropic responsiveness to cholinergic stimulation in both in vitro and in vivo experiments, significantly (P < 0.0001), while either incubation of isolated atria with licofelone (a dual COX/5-LOX inhibitor) or injection of licofelone to animals could reverse it, completely (P < 0.01). Hydrocortisone (phospholipase A2 and COX-2 inhibitor) in vitro and in vivo (P < 0.001, P < 0.05, respectively) as well as indomethacin (COX inhibitor) in vitro and in vivo (P < 0.05, P < 0.01, respectively) exerted some lesser effects.
Our data revealed that in endotoxemic rats, chronotropic hyporesponsiveness to cholinergic stimulation was modulated by the dual COX/5-LOX inhibitor licofelone, and this effect is comparable with hydrocortisone and indomethacin.]]></description><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Arachidonate 5-Lipoxygenase - metabolism</subject><subject>Carbachol - pharmacology</subject><subject>Cholinergic Agents - pharmacology</subject><subject>Chronotropic response</subject><subject>Cyclooxygenase</subject><subject>Cyclooxygenase Inhibitors - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Endotoxin</subject><subject>Endotoxins</subject><subject>Heart Atria - drug effects</subject><subject>Heart Rate - drug effects</subject><subject>Hydrocortisone - pharmacology</subject><subject>Indomethacin - pharmacology</subject><subject>Licofelone</subject><subject>Lipopolysaccharides</subject><subject>Lipoxygenase</subject><subject>Lipoxygenase Inhibitors - pharmacology</subject><subject>Male</subject><subject>Parasympathetic Nervous System - drug effects</subject><subject>Pyrroles - pharmacology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Systemic inflammation</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUhS0EokPhDRDKkkUz9W8m3iChij9pJDawthznpnNHiR1sZ9R5IN6zHqV0ycq-vufcI9-PkPeMbhllze1xC8f5YOOWU16edkI1-gXZsHana7pj_CXZUMpkzbXWV-RNSkdKqdJcvSZXgmupldYb8nePLgwwBg83la36xY6VO7sxhIfzPXib4FbVI87PZYX-gB3mEG-qCCeICVIFvg85PKCv0feLg77CabYYy8XmiJeZhxh8yDHM6IovzcEnPIGHlKocSjuM6CHel27KOC2jzRh8CauizekteTXYMcG7p_Oa_P765dfd93r_89uPu8_72omG53pgTascQNuwlslSqUEoLrjTTnZtp5Wy0jJOBYNB9AM4XbQDNCA65uxuENfk4zp3juHPAimbCZODcbQewpIMl1KKVjKli1SuUhdDShEGM0ecbDwbRs0FkDmaFZC5ADIroGL78JSwdBP0z6Z_RIrg0yqA8s8TQjTJIfiy07JOl00f8P8Jj6WhqaA</recordid><startdate>20201115</startdate><enddate>20201115</enddate><creator>Nikoui, Vahid</creator><creator>Mehrzadi, Saeed</creator><creator>Khan, Muhammad Imran</creator><creator>Aman, Waqar</creator><creator>Ostadhadi, Sattar</creator><creator>Dehpour, Ahmad Reza</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20201115</creationdate><title>Licofelone, a dual cyclooxygenase/5-lipoxygenase inhibitor, reverses endotoxin-induced impaired atrial chronotropic responsiveness to cholinergic stimulation in rats</title><author>Nikoui, Vahid ; Mehrzadi, Saeed ; Khan, Muhammad Imran ; Aman, Waqar ; Ostadhadi, Sattar ; Dehpour, Ahmad Reza</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-f1685cee861814f165f35232c9c4b8b955a4a12031ef3dfec9ee8fe6e3b1ca7f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Arachidonate 5-Lipoxygenase - metabolism</topic><topic>Carbachol - pharmacology</topic><topic>Cholinergic Agents - pharmacology</topic><topic>Chronotropic response</topic><topic>Cyclooxygenase</topic><topic>Cyclooxygenase Inhibitors - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Endotoxin</topic><topic>Endotoxins</topic><topic>Heart Atria - drug effects</topic><topic>Heart Rate - drug effects</topic><topic>Hydrocortisone - pharmacology</topic><topic>Indomethacin - pharmacology</topic><topic>Licofelone</topic><topic>Lipopolysaccharides</topic><topic>Lipoxygenase</topic><topic>Lipoxygenase Inhibitors - pharmacology</topic><topic>Male</topic><topic>Parasympathetic Nervous System - drug effects</topic><topic>Pyrroles - pharmacology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Systemic inflammation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nikoui, Vahid</creatorcontrib><creatorcontrib>Mehrzadi, Saeed</creatorcontrib><creatorcontrib>Khan, Muhammad Imran</creatorcontrib><creatorcontrib>Aman, Waqar</creatorcontrib><creatorcontrib>Ostadhadi, Sattar</creatorcontrib><creatorcontrib>Dehpour, Ahmad Reza</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nikoui, Vahid</au><au>Mehrzadi, Saeed</au><au>Khan, Muhammad Imran</au><au>Aman, Waqar</au><au>Ostadhadi, Sattar</au><au>Dehpour, Ahmad Reza</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Licofelone, a dual cyclooxygenase/5-lipoxygenase inhibitor, reverses endotoxin-induced impaired atrial chronotropic responsiveness to cholinergic stimulation in rats</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2020-11-15</date><risdate>2020</risdate><volume>887</volume><spage>173569</spage><epage>173569</epage><pages>173569-173569</pages><artnum>173569</artnum><issn>0014-2999</issn><eissn>1879-0712</eissn><abstract><![CDATA[Evidence show that endotoxemia is linked with tachycardia. The exact mechanism of tachycardia is not well-understood, but it seems that impaired cardiac chronotropic responsiveness to cholinergic stimulation plays a role in this phenomenon. The aim of this experiment was to study the effect of licofelone as a dual cyclooxygenase (COX)/5-lipoxygenase (5-LOX) inhibitor in modulation of atrial chronotropic hyporesponsiveness to cholinergic stimulation in endotoxemic rats, compared with hydrocortisone and indomethacin in in vitro and in vivo studies. Rats were injected by either of lipopolysaccharide (LPS) or saline. The isolated atria were incubated with licofelone, hydrocortisone, or indomethacin in an organ bath set up. In a separate experiment, rats were injected with licofelone, hydrocortisone, or indomethacin prior to isolation of the atria. Then, in both experiments, chronotropic responsiveness to cumulative concentrations of carbacholine in organ bath was recorded. LPS injection decreased the chronotropic responsiveness to cholinergic stimulation in both in vitro and in vivo experiments, significantly (P < 0.0001), while either incubation of isolated atria with licofelone (a dual COX/5-LOX inhibitor) or injection of licofelone to animals could reverse it, completely (P < 0.01). Hydrocortisone (phospholipase A2 and COX-2 inhibitor) in vitro and in vivo (P < 0.001, P < 0.05, respectively) as well as indomethacin (COX inhibitor) in vitro and in vivo (P < 0.05, P < 0.01, respectively) exerted some lesser effects.
Our data revealed that in endotoxemic rats, chronotropic hyporesponsiveness to cholinergic stimulation was modulated by the dual COX/5-LOX inhibitor licofelone, and this effect is comparable with hydrocortisone and indomethacin.]]></abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>32949599</pmid><doi>10.1016/j.ejphar.2020.173569</doi><tpages>1</tpages></addata></record> |
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| subjects | Animals Anti-Inflammatory Agents - pharmacology Arachidonate 5-Lipoxygenase - metabolism Carbachol - pharmacology Cholinergic Agents - pharmacology Chronotropic response Cyclooxygenase Cyclooxygenase Inhibitors - pharmacology Dose-Response Relationship, Drug Endotoxin Endotoxins Heart Atria - drug effects Heart Rate - drug effects Hydrocortisone - pharmacology Indomethacin - pharmacology Licofelone Lipopolysaccharides Lipoxygenase Lipoxygenase Inhibitors - pharmacology Male Parasympathetic Nervous System - drug effects Pyrroles - pharmacology Rats Rats, Wistar Systemic inflammation |
| title | Licofelone, a dual cyclooxygenase/5-lipoxygenase inhibitor, reverses endotoxin-induced impaired atrial chronotropic responsiveness to cholinergic stimulation in rats |
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