الفهرس 
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Abstract
Hepatic Fibrosis Is A Common Pathological Consequence Of All chronic Liver Diseases And Responsible For Significant Morbidity And Mortality Worldwide. Hepatic Stellate Cells (Hscs) Activation Plays A Significant Role In The Pathogenesis Of Hepatic Fibrosis. For Instance, Thioacetamide (TAA) Induces Hepatocyte Damage Via Its Metabolite, Causing DNA Damage And Lipid Peroxidation. Because Of The Role Of Oxidative Stress In Liver Fibrosis, Antioxidants Have Been Proposed As Protective Candidates Against Induced Liver Injury By Reducing Oxidative Stress In Cells. Phenolic Compounds Such As Gallic Acid And Ferulic Acid Process A Lot Of Biological Activities. Micrornas Are Small Non-Coding RNA Particles That Have Significant Roles In Cell Differentiation, Proliferation And Carcinogenesis. Particularly In The Liver, Several Micrornas Have Been Identified As Either Profibrotic Or Antifibrotic Molecules.
In The Present Study, We Evaluate The Possible Protective Effects Of Gallic Acid And Ferulic Acid Against An Experimentally Induced Liver Fibrosis In Rats By Thioacetamide In Comparison With Standard Drug; Silymarin. The Effect On TGF-Β1 /Smad3 Signaling Pathway And The Expression Levels Of Mirna-21, Mirna-30 And Mirna-200 Were Evaluated.Animals Were Divided Into 7 Groups: Control Group, Gallic Acid (GA) group (20 Mg/Kg/Day, P.O), Ferulic Acid (FA) group (20 Mg/Kg/Day, P.O), Thioacetamide (TAA) group (Receiving 250 Mg/Kg Twice /Week, I.P), (GA+ TAA ) Group, (FA + TAA) group (Received The Same Previous Dose) And (Silymarin +TAA) group (Received Silymarin At 100 Mg/Kg /Day + TAA As Mentioned Above) These Drugs Were Administrated Orally On A Daily Basis For 6 Consecutive Weeks from The First Day Prior To TAA Administration.
Animals Were Sacrificed And The Degree Of Hepatic Injury And Fibrosis Was Assessed By Measuring Liver Functions Such As Serum Activities Of Alanine Transaminase (ALT) And Aspartate Transaminase (AST) , Alkaline Phosphatase (ALP), Serum Levels Of Albumin, Total , Direct And Indirect Bilirubin. In Addition, Hepatic Content Of Malondialdehyde And Hepatic Activity Of Super Oxide Dismutase (SOD) As Well As Catalase (CAT) Were Measured As Oxidative Stress Biomarkers. Moreover, Hepatic Transforming Growth Factor Β1 (TGF-Β1) And Smad3 Were Measured As Fibrosis Markers. Additionally, Histopathological Examination By H And E As Well As Masson Trichrome Staining Of The Liver Tissues Were Performed To Confirm Biochemical Findings. Finally, Assessment Of Microrna Expression Of Micro RNA- 21, Microrna- 30 And Microrna 200 By Quantitative Real Time- Polymerase Chain Reaction (Qrt-Tpcr) Were Performed To Evaluate The Profibrotic Or Antifiboric Effect.
The Current Study Showed That, Administration Of TAA Significantly Elevated Serum ALT, AST, ALP In Addition To Total, Direct And Indirect Bilirubin While Serum Albumin Was Significantly Decreased As Compared To The Normal Animals. TAA Also Significantly Increased Hepatic MDA , TGF-Β1 And Smad3 While Hepatic CAT And SOD Activities Were Significantly Decreased. Histopathological Changes Like Inflammatory Infiltration, Blood Congestion, Loss Of Normal Hepatic Architecture And Deposition Of Collagen Content Were Observed. Besides, Mirna-21 Expression Was Upregulated While Mirna -30 And -200 Expressions Were Downregulated. Interestingly, The Results Showed That Administration Of Gallic Acid Or Ferulic Acid With TAA Induced A Significant Reduction In Activities Of Liver Enzymes While Increasing Plasma Albumin Concertation And Protected The Integrity Of Liver Tissues. Furthermore, They Increased The Activities Of The Hepatic Antioxidant Enzymes; Superoxide Dismutase And Catalase While Decreased Malondialdehyde Content To A Normal Level. The Hepatic Expression Of TGF-Β1 And Smad3 Proteins Were Significantly Decreased. In Addition, Mirna-21 Expression Was Downregulatead While Mirna -30 And -200 Expressions Were Upregulated By Administration Of Gallic Acid Or Ferulic Acid.
In Conclusion, Gallic Acid And Ferulic Acid Exhibit Antifibrotic And Antioxidant Effects Against TAA-Induced Liver Fibrosis In Rats. These Effects Are Mediated Through Inhibition Of TGF-Β /Smad3 Signaling Pathway In Addition To Differentially Affecting The Hepatic Expression Level Of Mirna- 21, Mirna-30 And Mirna -200.