Endotoxin-induced liver damage in rats is minimized by β2- adrenoceptor stimulation
article
Objective and Design: To investigate the effects of β2- adrenoceptor (β2-AR) stimulation on endotoxin-induced liver damage and systemic cytokine levels in rats. Subjects: Standard male Wistar rats. Treatment: A disease-model of lipolysaccharide (LPS)-induced acute systemic inflammation was used. The β2-selective AR agonist clenbuterol was administered before, during, and after LPS-challenge to investigate its effects on the acute inflammatory response and associated liver-failure. Methods: The following parameters have been measured in plasma: TNFα, IL-1β, IL-6, IL-10, AST, ALT, and Bilirubin. Liver histological examination was performed to look for changes in tissue morphology. Results: Administration of clenbuterol (p.o.) one hour before, or intravenous at the same time as LPS-challenge resulted in a marked reduction of plasma levels of TNFα, IL-1β, and IL-6. A change both in plasma-level and in time-concentration profile of the anti-inflammatory cytokine IL-10 was found. Clenbuterol minimized LPS-induced liver damage, as represented by significantly lowered concentrations of several parameters for liver-failure (AST, ALT, Bilirubin), and improved hepatic tissue morphology. Clenbuterol administration after LPS challenge failed to inhibit TNFα-release but reduced liver-damage. Simultaneous use of the β2-AR antagonist propranolol augmented LPS-induced liver failure, suggesting a role of endogenous adrenoceptor-agonists in prevention of organ-failure during systemic inflammation. Conclusions: The results indicate that a selective β2-AR agonist might be used as an additional therapeutic agent in the clinic for the treatment of (acute) systemic inflammatory disorders in order to reduce or prevent subsequent liver failure.
Topics
Physiological SciencesAdrenoceptor agonistsCytokinesEndotoxemiaImmunopharmacologyLiver-failureAlanine aminotransferaseAspartate aminotransferaseBeta adrenergic receptorBilirubinClenbuterolCytokineEndotoxinInterleukin 10Interleukin 1betaInterleukin 6LipopolysaccharidePropranololTumor necrosis factor alphaAnimal modelAnimal tissueControlled studyEnzyme linked immunosorbent assayLiver failureLiver injuryMaleNonhumanRatAdrenergic beta-AgonistsAdrenergic beta-AntagonistsAlanine TransaminaseAnimalsAspartate AminotransferasesClenbuterolEndotoxinsInflammationInterleukin-1Interleukin-10Interleukin-6LipopolysaccharidesLiverLiver FailureMaleOsmolar ConcentrationPropranololRatsRats, WistarTumor Necrosis Factor-alpha
TNO Identifier
237663
ISSN
10233830
Source
Inflammation Research, 53(3), pp. 93-99.
Pages
93-99
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