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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 392, Issue 1, pp 37–43 | Cite as

Targeting HMGB1/TLR4 axis and miR-21 by rosuvastatin: role in alleviating cholestatic liver injury in a rat model of bile duct ligation

  • Enas S. NabihEmail author
  • Omnyah A. El-kharashi
Original Article
  • 90 Downloads

Abstract

Many pathways are involved in the association between biliary obstruction and liver injury. We investigated the intervention influence and effect of rosuvastatin (Rvs) on the high mobility group protein 1 (HMGB1)/toll-like receptor-4 (TLR4) axis and microRNA-21 (miR-21) in cholestatic liver injury. This model was performed by ligating common bile duct of Wistar rats. Saline and Rvs were orally administrated by gastric gavages. Liver and blood samples were collected and subjected to molecular and biochemical evaluation. We found that the daily oral administration of Rvs was protective against the occurrence of cholestatic liver injury. This was evident from the results of hepatic, oxidative stress, and inflammatory biomarkers. This study also revealed the Rvs inhibitory effect on the HMGB1/TLR4 intracellular signaling axis as evidenced by decreasing the levels of nuclear factor κβ (NFκβ), tumor necrosis factor α (TNFα), and interleukin 6 (IL6) production. Furthermore, Rvs-treated group showed a significant reduction in the expression of miR-21 in comparison to the untreated group. Accordingly, rosuvastatin interference with the HMGB1/TLR4 and miR-21 expression could explain its hepatoprotective effect in cholestatic liver injury.

Keywords

Cholestasis HMGB1 miR-21 Rosuvastatin TLR4 

Abbreviations

ALP

Alkaline phosphatase

ALT

Alanine transaminase

AST

Aspartate transaminase

BDL

Bile duct ligation

GGT

γ-Glutamyltransferase

HCC

Hepatocellular carcinoma

HMGB1

High mobility group protein 1

IL6

Interleukin 6

MDA

Malondialdehyde

miR-21

MicroRNA-21

NFκβ

Nuclear factor κβ

PCR

Polymerase chain reaction

ROS

Reactive oxygen species

Rvs

Rosuvastatin

Stat3

Signal transducer and activator of transcription 3

TLR4

Toll-like receptor-4

Notes

Author contributions

Enas S. Nabih: Share in idea, design, biochemical work, and writing the manuscript.

Omnyah A. El-Kharashi: Share in idea, design, pharmacological work, and writing the manuscript.

Compliance with ethical standards

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Medical Biochemistry and Molecular Biology, Faculty of MedicineAin Shams UniversityCairoEgypt
  2. 2.Department of Clinical Pharmacology, Faculty of MedicineAin Shams UniversityCairoEgypt

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