Licofelone, a dual cyclooxygenase/5-lipoxygenase inhibitor, reverses endotoxin-induced impaired atrial chronotropic responsiveness to cholinergic stimulation in rats

Copyright © 2020 Elsevier B.V. All rights reserved..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:887

Enthalten in:

European journal of pharmacology - 887(2020) vom: 15. Nov., Seite 173569

Sprache:

Englisch

Beteiligte Personen:

Nikoui, Vahid [VerfasserIn]
Mehrzadi, Saeed [VerfasserIn]
Khan, Muhammad Imran [VerfasserIn]
Aman, Waqar [VerfasserIn]
Ostadhadi, Sattar [VerfasserIn]
Dehpour, Ahmad Reza [VerfasserIn]

Links:

Volltext

Themen:

8Y164V895Y
Anti-Inflammatory Agents
Arachidonate 5-Lipoxygenase
Carbachol
Cholinergic Agents
Chronotropic response
Cyclooxygenase
Cyclooxygenase Inhibitors
EC 1.13.11.34
Endotoxin
Endotoxins
Hydrocortisone
Indomethacin
Journal Article
Licofelone
Lipopolysaccharides
Lipoxygenase
Lipoxygenase Inhibitors
P5T6BYS22Y
Pyrroles
Systemic inflammation
WI4X0X7BPJ
XXE1CET956

Anmerkungen:

Date Completed 14.05.2021

Date Revised 14.05.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.ejphar.2020.173569

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM315209739