الفهرس 
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Abstract
This Study Was Designed To Clarify The Role Of XO-JAK-STAT Signaling Pathway In Test-Induced BPH. Moreover, Studying The Possible Modulatory Effects Of Feb And CNMA As A Promising Treatment Strategy In BPH. To Achieve The Objectives Of This Study, Two Experiments Were Set, Experiment (I) Was On Feb, And Experiment (II) Was On CNMA.
Experimentally, The Induction Of BPH Was Carried Out Via Test (3 Mg/Kg, S.C.) For Two Consecutive Weeks. Each Experiment Was Divided Into Four Major Sets As Follow: Control Group, Feb (10 Mg/Kg) Or CNMA (40 Or 75 Mg/Kg) Group, Test-Treated group (3 Mg/Kg), The Last group Received Feb Or CNMA And Then Test Was Added 5 Days Later. For Evaluation Of Serum Level Of UA, Blood Samples Were Withdrawn from The Retro-Orbital Plexus Of Each Animal Under Anesthesia 72 H After The Last Test Injection.
For Investigation Of Prostate Tissues, Rats Were Sacrificed By Decapitation And Prostate Tissues Were Rapidly Dissected Out For Morphological Assessment And Weighing. Portion Of Prostatic Tissue Was Fixed In Neutral Buffered Formalin (10%) For Histological And Immunohistochemical Examination Of Cyclin D1. The Remaining Tissue Was Stored At -80 ºc For JAK-1 And P-STAT-3 Western Blot Analysis, Examination Of Bax And Bcl-2 Mrna Expressions By Qrt-PCR, Assessment Of XO Activity, Oxidative Stress Biomarkers (GSH, SOD, MDA) And Inflammatory Markers (IL-6, IL-1β, TNF-Α, NF Κb).
Results Of The Present Work Can Be Summarized As Follows:
A) Effects Of Febuxostat (Feb) On Testosterone (Test)-Induced BPH In Rats:
Treatment With Feb Significantly Reduced The Prostatic Weight And Index Compared To Test-Treated Group.
Treatment With Feb Significantly Ameliorated The Increase In XO Activity In Prostatic Tissue And Serum Level Of UA Induced Via Test.
Treatment With Feb Markedly Ameliorated Oxidative Stress As It Reduced Lipid Peroxidation And Prevented The Exhaustion Of SOD Activity And GSH Depletion Induced By Test.
Treatment With Feb Obviously Reduced Prostate Contents Of IL-6, IL-1β, TNF-Α And NF Κb Compared To Test-Treated Group.
Treatment With Feb Clearly Reduced The Protein Expression Of JAK-1 And The Subsequent Phosphorylation Of STAT-3 Protein Induced Via Test.
Treatment With Feb Markedly Ameliorated The Pathological Changes Of Prostatic Tissues Induced Via Test.
Treatment With Feb Obviously Prevented The Rise In Cyclin D1 Protein Expression Induced By Test.
Treatment With Feb Clearly Enhanced Bax/Bcl2 Mrna Ratio Compared To Test-Treated Group.
B) Effects Of Cinnamaldehyde (CNMA) On Testosterone (Test)-Induced BPH In Rats:
Treatment With CNMA Significantly Reduced The Prostatic Weight And Index Compared To Test-Treated Group.
Treatment With CNMA Significantly Ameliorated The Increase In XO Activity In Prostatic Tissue And Serum Level Of Uric Acid Induced Via Test.
Treatment With CNMA Markedly Ameliorated Oxidative Stress As It Reduced Lipid Peroxidation And Prevented The Exhaustion Of SOD Activity And GSH Depletion Induced By Test.
Treatment With CNMA Obviously Reduced Prostate Contents Of IL-6, IL-1β, TNF-Α And NF Κb Compared To Test- Treated Group.
Treatment With CNMA Clearly Reduced The Protein Expression Of JAK-1 And The Subsequent Phosphorylation Of STAT-3 Protein Induced Via Test.
Treatment With CNMA Markedly Ameliorated The Pathological Changes Of Prostatic Tissues Induced Via Test.
Treatment With CNMA Obviously Prevented The Rise In Cyclin D1 Protein Expression Induced By Test.
Treatment With CNMA Clearly Enhanced Bax/Bcl2 Mrna Ratio Compared To Test-Treated Group.
In Conclusion, Test Can Induce BPH Via Activation Of XO/JAK-1/STAT-3 Axis. In Contrast, The Uric Acid Lowering Agent Feb Protects Against Test-Induced BPH In Rats. Similarly, CNMA Which Is A Natural XO Inhibitor Having Anti-Oxidant, Anti-Inflammatory And Anti-Proliferative Activities Guarded Against Test-Induced BPH. These Protective Effects Of Both Compounds Could Be Explained, At Least In Part, By Their Suppression Of XO/ JAK-1/ STAT-3 Axis. They Significantly Reduced NF-Κb Activation And Nuclear Translocation, Which Eventually Leads To Decreased Release Of Inflammatory Mediators. Consequently, Both Compounds Reduced The Expression Of JAK-1 Protein Which Is Linked To IL-6 Receptors And Finally Reduced The Activation Of STAT-3 Protein And Subsequent Prostatic Cell Proliferation (Figure 6.1).
The Results Of The Current Study Suggested That Hyperuricemia Is A Key Player In Test-Induced BPH Which May Shade Light On A New Promising Therapeutic Strategy Against Benign Prostatic Hyperplasia Using Feb And/Or CNMA.
Figure 6.1: Schematic Diagram Of The Proposed Mechanisms Of Febuxostat (Feb) And Cinnamaldehyde (CNMA) Protective Effect Against Testosterone (Test)-Induced Prostatic Hyperplasia In Rats.