Diacerein protects rats with liver ischemia/reperfusion damage: Down-regulation of TLR4/ NFκ-B signaling pathway

• Published in: Biomedicine & pharmacotherapy Vol. 134; p. 111063
• Main Authors: Ibrahim, Mohamed Abdellah, Abdelzaher, Walaa Yehia, Ibrahim, Yasmine F., Ahmed, Amira F., Welson, Nermeen N., Al-Rashed, Sarah, Batiha, Gaber El-Saber, Abdel-Aziz, Asmaa Mohamed
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01-02-2021; Elsevier
• Subjects: Alanine Transaminase - metabolism; Animals; Anthraquinones - pharmacology; Anti-Inflammatory Agents - pharmacology; Antioxidants - pharmacology; Diacerein; Down-Regulation; Fatty Acid-Binding Proteins - metabolism; Inflammatory pathway; L-FABP; Liver - drug effects; Liver - metabolism; Liver Diseases - drug therapy; Liver Diseases - pathology; Liver ischemia-reperfusion; Male; NF-kappa B - metabolism; Oxidative Stress - drug effects; Protective Agents - pharmacology; Rats; Reperfusion Injury - drug therapy; Reperfusion Injury - pathology; Signal Transduction - drug effects; Toll-Like Receptor 4 - metabolism; Tumor Necrosis Factor-alpha - metabolism; Vascular Cell Adhesion Molecule-1 - metabolism; L-FABP; Inflammatory pathway; Liver ischemia-reperfusion; Diacerein
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2020.111063

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•Liver ischemia reperfusion injury is an unavoidable problem, still a challenge.•Diacerein exhibits anti-inflammatory, anti-apoptotic and antioxidant properties.•Liver fatty acid binding protein, an effective marker to detect early liver damage.•Adhesion molecule accepted to be a cornerstone in ischemia reperfusion injury.•Diacerein could ameliorate the signaling mechanisms underlying this pathophysiology.
Liver ischemia-reperfusion (I/R) injury is an inescapable problem. Diacerein, a chondro-protective drug, has antioxidant and anti-inflammatory effects. Its effect on liver I/R injury has not yet been fully clarified. Therefore, the current study aimed to detect its hepatic protective effect with the explanation of possible underlying mechanisms.
Adult male albino rats were assigned to 4 groups: sham group, diacerein pretreated sham group, I/R non-treated group, and I/R diacerein pretreated group. Serum liver enzymes, hepatic tissue oxidative stress parameters, inflammatory biomarkers mainly Toll-like receptors-4 (TLR4), and liver fatty acid binding protein (L-FABP) levels were determined. Histopathological examination of liver tissues and immunohistochemical studies of heat shock protein 70, nuclear factor-kappa B, and Cluster of Differentiation 68 were also done.
Diacerein pretreatment has the ability to restore the hepatic I/R damaging effect, proved by the reduction of serum liver enzymes, the decrease of the oxidative stress and hepatic inflammation via down-regulation of TLR4/ NFκ-B signaling pathway together with the restoration of L-FABP level and improvement of the histopathological and immunohistochemical study findings in the hepatic tissue.
These results suggested the hepatoprotective effect of diacerein relies on its antioxidant and anti-inflammatory effects reducing TLR4/ NFκ-B signaling pathway.