Plumbagin ameliorates hepatic ischemia-reperfusion injury in rats: Role of high mobility group box 1 in inflammation, oxidative stress and apoptosis

[Display omitted] •Plumbagin exerts a robust hepatoprotective activity against I/R-induced insults.•Plumbagin inhibits HMGB1 expression during reperfusion phase.•Plumbagin mitigates HMGB1-associated inflammation, oxidative burst and apoptosis. Ischemia-reperfusion (I/R) injury is a pathological proc...

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Bibliographic Details
Published in:Biomedicine & pharmacotherapy 2018-10, Vol.106, p.785-793
Main Authors: Zaki, Aya M., El-Tanbouly, Dalia M., Abdelsalam, Rania M., Zaki, Hala F.
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents - pharmacology
Antioxidants - pharmacology
Apoptosis
Apoptosis - drug effects
Biomarkers - blood
Cytoprotection
Disease Models, Animal
Enzymes - blood
Glutathione - metabolism
Glutathione Peroxidase - metabolism
Hepatitis - metabolism
Hepatitis - pathology
Hepatitis - prevention & control
HMGB1
HMGB1 Protein - metabolism
Inflammation
Inflammation Mediators - blood
Ischemia-reperfusion
Lipid Peroxidation - drug effects
Liver
Liver - drug effects
Liver - metabolism
Liver - pathology
Male
Naphthoquinones - pharmacology
Oxidative stress
Oxidative Stress - drug effects
Plumbagin
Rats, Wistar
Reactive Oxygen Species - metabolism
Reperfusion Injury - metabolism
Reperfusion Injury - pathology
Reperfusion Injury - prevention & control
Signal Transduction - drug effects
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Summary:[Display omitted] •Plumbagin exerts a robust hepatoprotective activity against I/R-induced insults.•Plumbagin inhibits HMGB1 expression during reperfusion phase.•Plumbagin mitigates HMGB1-associated inflammation, oxidative burst and apoptosis. Ischemia-reperfusion (I/R) injury is a pathological process which magnifies with the ensuing inflammatory response and endures with the increase of oxidants especially during reperfusion. The present study was conducted to assess the possible modulatory effects of plumbagin, the active constituent extracted from the roots of traditional medicinal plant Plumbago zeylanica L., on the dire role of high mobility group box 1 (HMGB1) as well as the associated inflammation, oxidative stress and apoptotic cell death following hepatic I/R. Four groups of rats were included: sham-operated, sham-operated treated with plumbagin, I/R (30 min ischemia and 1 h reperfusion) and I/R treated with plumbagin. Pretreatment with plumbagin markedly improved hepatic function and structural integrity compared to the I/R group, as manifested by depressed plasma transaminases and lactate dehydrogenase (LDH) activities as well as alleviated tissue pathological lesions. Plumbagin prominently hampered HMGB1 expression and subsequently quelled inflammatory cascades, as nuclear factor κB (NF-κB), tumor necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO) activity. It also interrupted reactive oxygen species (ROS)-HMGB1loop as evident by restored liver reduced glutathione (GSH), elevated glutathione peroxidase (GPx) activity, along with decreased liver lipid peroxidation. Simultaneously, plumbagin significantly ameliorated apoptosis by amending the mRNA expressions of both anti-apoptotic (Bcl-2) and pro-apoptotic (Bax). The present results revealed that plumbagin is endowed with hepatoprotective activity ascribed to its antioxidant, anti-inflammatory and anti-apoptotic properties which are partially mediated through dampening of HMGB1 expression.
ISSN:0753-3322
1950-6007
DOI:10.1016/j.biopha.2018.07.004