الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
In The Current Study, The Protective Effect Of Three Test Agents from Different Classes; The Anti-Oxidant Essential Oil Carvacrol, The Potassium Channel Opener Nicorandil And The Antidepressant Drug Venlafaxine With Different Mechanisms Of Action Were Tested In Controlling Bronchial Asthma Induced Experimentally In Rats In Comparison To Standard Drug Dexamethasone (1 Mg/Kg/Day).
For Induction Of Bronchial Asthma, Rats Were Exposed To Ovalbumin Intraperitonial Sensitization Dose (1 Ml Normal Saline Suspension Containing 200 µg Ovalbumin (OVA) And 10 Mg Al(OH)3) At Days 1,2,3 And 11). Then Rats Were Exposed To Intranasal Challenge Dose (300 µl Saline Containing 1.5 Mg OVA Through The Last Three Days Of The Experiment). The Test Agents Were Given Orally On A Daily Basis For 14 Consecutive Days Before The Challenge And Through The Three Days Of Challenge. Samples Of Blood, BALF And Lung Specimens Were Collected 24 H After The Last Challenge.
The Inflammation Severity And Airway Remodeling Were Estimated Based On The Assessment Of Absolute Eosinophil Count In BALF Pellets (AEC), Serum Level Of Immunoglobulin-E (Ige), T Helper 2 Cytokines; Interleukin-4, Interleukin-5 And Interleukin-13 (IL-4, -5, -13) In BALF And T Helper 1 Cytokines; Tumor Necrosis Factor-Alpha (TNF-Α), Interferon-Gamma (IFN-Γ) And Inducible Nitric Oxide Synthase (Inos) In BALF As Well As Oxidative Biomarkers; Superoxide Dismutase (SOD) Activity, Reduced Glutathione (GSH) And Malondialdehyde (MDA) Contents In Lung Tissue Homogenates. In Addition, Immunohistochemical Study Of Urocortin (UCN) And Western Blot Analysis Of Surfactant Protein-D (SP-D) Were Done. Finally, Lung Histopathological Study Was Performed To Support The Biochemical Results.
The Main Findings Of The Current Investigation Can Be Summarized As Follow:
1- Effect Of OVA On Normal Adult Male Rat:
• OVA Challenge Significantly Increased AEC In Pellets Of BALF As Compared To Normal Control Group.
• OVA Challenge Significantly Increased Ige Serum Level As Compared To The Normal Control Group.
• OVA Caused A Significant Elevation In IL-4, IL-5, IL-13, TNF-Α, IFN-Γ And Inos Levels In BALF As Compared To The Normal Control Group.
• OVA Challenge Significantly Exaggerated The Oxidative Status Evidenced By A Significant Reduction In SOD Activity And GSH Content And A Significant Elevation In MDA Content In Lung Homogenates As Compared To The Normal Control Group.
• Immunohistochemical Study Of The Asthmatic Rats Showed A Significant Increase In UCN Expression And The Western Blot Analysis Showed A Significant Increase In SP-D Expression In Lung Tissue As Compared To The Normal Control Group.
• Histopathological Study Of Lung Tissues Taken from Rats Subjected To OVA Showed Distortion Of The Bronchial And Alveolar Architecture And Exaggerated Peribronchial And Perivascular Cuffs With Severe Inflammatory Reactions.
2- Effect Of DEXA On OVA-Induced Bronchial Asthma:
• Pretreatment With DEXA Significantly Decreased AEC In Pellets Of BALF As Compared To Asthma Control Group.
• Pretreatment With DEXA Significantly Reduced Ige Serum Level As Compared To The Asthma Control Group.
• Pretreatment With DEXA Caused A Significant Reduction In IL-4, IL-5, IL-13, TNF-Α, IFN-Γ And Inos Levels In BALF As Compared To The Asthma Control Group.
• Pretreatment With DEXA Significantly Alleviated The Oxidative Status Evidenced By A Significant Elevation In SOD Activity And GSH Content And A Significant Reduction In MDA Content In Lung Tissue Homogenates As Compared To The Asthma Control Group.
• Immunohistochemical Study Of The Rats Pretreated With DEXA Showed A Significant Decrease In UCN Expression And Western Blot Analysis Also Showed A Remarkable Decrease In SP-D Expression In Lung Tissue As Compared To The Asthma Control Group.
• Histopathological Study Of Lung Tissues Taken from Rats Pretreated With DEXA Showed Remarkable Improvement In Inflammatory Reactions With Restoration To The Normal Lung Architecture.
3- Effect Of Carvacrol, Nicorandil And Venlafaxine On OVA-Induced Bronchial Asthma:
• Pretreatment With Carvacrol, Nicorandil And Venlafaxine Significantly Reduced AEC In Pellets Of BALF As Compared To The Asthma Control Group.
• Pretreatment With Carvacrol, Nicorandil And Venlafaxine Significantly Decreased Ige Serum Level As Compared To The Asthma Control Group.
• Pretreatment With Carvacrol, Nicorandil And Venlafaxine Caused A Remarkable Reduction In IL-4, IL-5, IL-13, TNF-Α, IFN-Γ And Inos Levels In BALF As Compared To The Asthma Control Group.
• Pretreatment With Carvacrol, Nicorandil And Venlafaxine Significantly Abrogated The Oxidative Status Evidenced By A Significant Increase In SOD Activity And GSH Content And A Significant Decrease In MDA Content In Lung Homogenates As Compared To The Asthma Control Group.
• Immunohistochemical Study Of Rats Pretreated With Carvacrol, Nicorandil And Venlafaxine Showed A Significant Decrease In UCN Expression And Western Blot Analysis Showed A Significant Decrease In SP-D Expression In Lung Tissue As Compared To The Asthma Control Group.
• Histopathological Study Of Lung Tissues Taken from Rats Pretreated With Carvacrol, Nicorandil And Venlafaxine Showed Significant Improvement In Inflammatory Reactions And Improved Lung Architecture.
Based On The Previous Findings, It Could Be Concluded That:
1- Ovalbumin Induced Bronchial Asthma In Experimental Rats Was Evidenced By Significant Increase In The Inflammatory And Immunological Markers As Well As Oxidative And Nitrosative Stress Biomarkers.
2- Carvacrol, Nicorandil And Venlafaxine Could Protect Against Bronchial Asthma Induced Experimentally In Rats To A Similar Extent As The Standard Drug DEXA Making Them A Potential Therapeutic Option In Prevention Of Asthma With Avoidance Of The Adverse Effects Of Corticosteroids.
3- The Most Probably Mechanisms For The Anti-Asthmatic Effects Of These Drugs Include, At Least Partially, Their Immunomodularory, Antiinflammatory And Antioxidant Effects Making Them To Be Promising In Asthma Protection. However, Further Clinical Trials Are Required To Illustrate The Feasibility Of Application Of These Drugs In Management Of Asthma.