4.6 Article

Chondroitin Sulfate Protects the Liver in an Experimental Model of Extra-Hepatic Cholestasis Induced by Common Bile Duct Ligation

Journal

MOLECULES
Volume 27, Issue 3, Pages -

Publisher

MDPI
DOI: 10.3390/molecules27030654

Keywords

liver; fibrosis; chondroitin; regeneration; apoptosis; inflammation

Funding

  1. Sao Paulo Research Foundation [FAPESP-MRN 2008/55928-0, 2017/00896-5]
  2. Coordination for the Improvement of Higher Education Personnel (CAPES-PG Scholarship)

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Chondroitin sulfate (CS) has been found to have therapeutic effects in an experimental model of bile duct ligation. CS reduces collagen content and increases liver parenchyma content, and can alter the hepatic collagen III/I ratio. Additionally, CS reduces cell death indicators and promotes regeneration. Therefore, CS has potential hepatoprotective action in fibrogenesis induced by bile duct ligation.
During liver fibrogenesis, there is an imbalance between regeneration and wound healing. The current treatment is the withdrawal of the causing agent; thus, investigation of new and effective treatments is important. Studies have highlighted the action of chondroitin sulfate (CS) in different cells; thus, our aim was to analyze its effect on an experimental model of bile duct ligation (BDL). Adult Wistar rats were subjected to BDL and treated with CS for 7, 14, 21, or 28 days intraperitoneally. We performed histomorphometric analyses on Picrosirius-stained liver sections. Cell death was analyzed according to caspase-3 and cathepsin B activity and using a TUNEL assay. Regeneration was evaluated using PCNA immunohistochemistry. BDL led to increased collagen content with corresponding decreased liver parenchyma. CS treatment reduced total collagen and increased parenchyma content after 21 and 28 days. The treatment also promoted changes in the hepatic collagen type III/I ratio. Furthermore, it was observed that CS treatment reduced caspase-3 activity and the percentage of TUNEL-positive cells after 14 days and cathepsin B activity only after 28 days. The regeneration increased after 14, 21, and 28 days of CS treatment. In conclusion, our study showed a promising hepatoprotective action of CS in fibrogenesis induced by BDL.

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