الفهرس 
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Abstract
The Liver Plays A Central Role In Transforming And Clearing Chemicals And Is Susceptible To The Toxicity from These Agents. Chemicals That Cause Liver Injury Are Called Hepatotoxins. 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 Damage, Antioxidants Have Been Proposed As Protective Candidates Against Liver Injury By Reducing Oxidative Stress In Cells. Natural Compounds Such As Chlorogenic Acid (CGA), Quercetin (Qt) And Co Enzyme Q10 (Q10) Are Involved In Many Biological Activities. The Keap1-Nrf2 Pathway Is A master Regulator Of The Antioxidant Response And The Major Regulator Of Cytoprotective Responses To Endogenous And Exogenous Stresses Caused By Reactive Oxygen Species (ROS) And Electrophiles. In The Present Study, We Evaluated The Possible Protective Effects Of Chlorogenic Acid, Quercetin And Co Enzyme Q10 Against An Experimentally Induced Liver Toxicity In Rats By Thioacetamide In Comparison With Standard Drug; Silymarin. The Effect On Keap1-Nrf2 Signaling Pathway And The Expression Of Heme Oxygenase -1 (HO-1) Was Evaluated. Animals Were Divided Into 13 Groups: Control, Silymarin, CGA, Qt, Q10, TAA (Single Dose 50 Mg/Kg, I.P.), TAA+Silymarin (400 Mg/Kg, P.O.), TAA+CGA (100 & 200 Mg/Kg, P.O.), TAA+Qt (200 &300 Mg/Kg, P.O.) And TAA+ Q10 (30&50 Mg/Kg, P.O.) And Treated For 8 Days from The First Day Prior To TAA Administration. Animals Were Sacrificed And The Degree Of Hepatic Injury Was Assessed By Measuring Liver Functions Such As Serum Activities Of Alanine Transaminase (ALT), Aspartate Transaminase (AST), Alkaline Phosphatase (ALP), Total , Direct And Indirect Bilirubin. In Addition, Hepatic Content Of Malondialdehyde (MDA), Nitric Oxide (NO) And Glutathione Content (GSH) In Addition To Hepatic Activity Of Super Oxide Dismutase (SOD) As Well As Were Measured As Oxidative Stress Biomarkers. Moreover, Hepatic Keap1/ Nrf2 Expressions And HO-1 Activity Were Measured. Additionally, Histopathological Examination By H And E Staining Of The Liver Tissues Was Performed To Confirm Biochemical Findings. Measuring The Number Of Apoptotic Cells By TUNEL Assay And The Expression Level Of Tumor Necrosis Factor -Α (TNF-Α) By Immunohistochemistry Were Assessed.
The Current Study Showed That Administration Of TAA Significantly Elevated Serum ALT, AST, ALP In Addition To Total, Direct And Indirect Bilirubin As Compared To The Normal Animals. TAA Also Significantly Increased Hepatic MDA And NO , While Hepatic GSH And SOD Activities Were Significantly Decreased. Histopathological Changes Like Inflammatory Infiltration, Blood Congestion, Loss Of Normal Hepatic Architecture Were Observed. Besides, Western Blot Analysis Showed That Keap1 Expression Was Significantly Increased While Nrf2 Expression And HO-1 Activity Were Decreased. Moreover, The Number Of Apoptotic Cells And TNF-Α Expression Were Increased In TAA group Compared To The Normal group Interestingly, The Results Showed Improved Activities Of Liver Functions And A Protection Of The Integrity Of Liver Tissues In TAA+Silymarin, TAA+CGA, TAA+Qt And TAA+Q10 Groups Compared To The TAA Group. Furthermore, These Groups Showed Significantly Lower MDA And NO Levels But Higher GSH Content And SOD Activity Compared To The TAA Group. Remarkably, Keap1 Expression Was Significantly Decreased While Nrf2 Expression And HO-1 Activity Were Increased. The Expression Level Of TNF-Α And The Number Of Apoptotic Cells Were Also Decreased. In Conclusion, CGA, Qt, Q10 And Silymarin Protect Against TAA-Induced Acute Liver Toxicity Via Antioxidant, Anti-Inflammatory And Anti-Apoptotic Activities And Regulating Keap1-Nrf2/HO-1 Expression. Finally, TAA Caused An Acute Liver Toxicity In Rats Through Stimulating The Inflammatory Mediators And Oxidative Stress. This Study Demonstrated The Ability Of Chlorogenic Acid, Quercetin ,Coenzyme Q10 To Protect Against TAA-Induced Acute Liver Toxicity To Degrees Similar To Or Better Than That Of The Reference Drug; Silymarin Making Them Potential Therapeutic Options To Prevent Acute Liver Toxicity. The Hepatoprotective Effects Are, At Least Partly, Due To Their Antioxidant, Anti-Inflammatory, Anti-Apoptotic Properties Via The Inhibition Of Oxidative Stress And Stimulating Keap1-Nrf2 Signaling That Subsequently Lead To Increasing HO-1 Expression.