Abstract
Sepsis induces hepatic injury but whether alpha-2 adrenoceptor (α2-AR) modulates the severity of sepsis-induced liver damage remains unclear. The present study used lipopolysaccharide (LPS) to induce hepatic injury and applied α2-AR agonist dexmedetomidine (DEX) and/or antagonist yohimbine to investigate the contribution of α2-AR in LPS-induced liver injury. Our results showed that LPS resulted in histological and functional abnormality of liver tissue (ALT and AST transaminases, lactate), higher mortality, an increase in proinflammatory cytokines (IL-1β, IL-6 & TNF-α), as well as a change in oxidative stress (MDA, SOD). Activation of α2-AR by dexmedetomidine (DEX) attenuated LPS-induced deleterious effects on the liver and block of α2-AR by yohimbine aggravated LPS-induced liver damage. Our data suggest that α2-AR plays an important role in sepsis-induced liver damage and activation of α2-AR with DEX could be a novel therapeutic avenue to protect the liver against sepsis-induced injury.
Keywords:
Sepsis; dexmedetomidine; liver injury; yohimbine; α2-adrenoceptor agonist.
MeSH terms
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Adrenergic alpha-2 Receptor Agonists / pharmacology*
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Adrenergic alpha-2 Receptor Antagonists / pharmacology
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Alanine Transaminase / blood
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Animals
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Aspartate Aminotransferases / blood
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Biomarkers / blood
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Chemical and Drug Induced Liver Injury / blood
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Chemical and Drug Induced Liver Injury / etiology
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Chemical and Drug Induced Liver Injury / pathology
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Chemical and Drug Induced Liver Injury / prevention & control*
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Cytoprotection
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Dexmedetomidine / pharmacology*
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Disease Models, Animal
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Interleukin-1beta / metabolism
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Interleukin-6 / metabolism
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Lactic Acid / blood
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Lipopolysaccharides*
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Liver / drug effects*
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Liver / metabolism
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Liver / pathology
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Male
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Malondialdehyde / metabolism
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Oxidative Stress / drug effects
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Rats, Sprague-Dawley
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Receptors, Adrenergic, beta-2 / drug effects*
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Receptors, Adrenergic, beta-2 / metabolism
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Sepsis / chemically induced
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Superoxide Dismutase / metabolism
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Time Factors
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Tumor Necrosis Factor-alpha / metabolism
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Yohimbine / pharmacology
Substances
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Adrenergic alpha-2 Receptor Agonists
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Adrenergic alpha-2 Receptor Antagonists
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Biomarkers
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IL1B protein, rat
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Interleukin-1beta
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Interleukin-6
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Lipopolysaccharides
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Receptors, Adrenergic, beta-2
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Tumor Necrosis Factor-alpha
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lipopolysaccharide, Escherichia coli O111 B4
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Yohimbine
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Lactic Acid
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Malondialdehyde
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Dexmedetomidine
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Superoxide Dismutase
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Aspartate Aminotransferases
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Alanine Transaminase