الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
In The Present Study, The Protective Effect Of Three Tested Drugs, Namely Allopurinol, Rosiglitazone And Fluoxetine, In Two Dose Levels Was Investigated In Controlling Bronchial Asthma Symptoms Experimentally Induced In Rats As Compared To Reference Standard Treatment Dexamethasone (DEXA) In A Dose Of 1 Mg/Kg/Day.
Bronchial Asthma Was Induced Experimentally In Rats By OVA Challenge. Briefly, Rats Were Sensitized Intraperitoneally With 200 µg OVA/10 Mg Al (OH)3 For Each Rat At Days 1, 2, 3 And 11. Rats Were Then Intranasally Challenged With 300 µl Saline Containing 1.5 Mg OVA At Days 20, 21 And 22. The Effect Was Studied After Administration Of The Tested Drugs For 2 Weeks Before Challenge And During 3 Days Of Challenge. Blood Samples, BAL Fluid And Lung Samples Were Collected 24 H After The Last Challenge.
Firstly, The Protective Effect Of The Tested Drugs Was Evaluated Based On Estimation Of Respiratory Functions, Namely Tidal Volume (TV) And Peak Expiratory Flow Rate (PEFR) Tests, Serum Immunoglobulin E (Ige), Total Nitrate/Nitrite (Nox) Level In BAL Fluid. Additionally, Inflammatory Cytokines Parameters As Tumor Necrosis Factor-Alpha (TNF-Α) And Interleukin-4 (IL-4) Levels In Lung Homogenates Were Estimated. Oxidative Stress Biomarkers As Reduced Glutathione (GSH), Malondialdehyde (MDA) Levels And Superoxide Dismutase (SOD) Activity In Lung Homogenates Were Also Evaluated. Also, Histopathological Examination Of Lung Sections Was Conducted.
Secondly, Additional Parameters Were Measured To Assess The Role Of Fluoxetine In Managing Asthma- Associated Depression. Behavioral Tests Including Open Field Test And Forced Swimming Test Were Performed. Additionally, Brain-Derived Neurotrophic Factor (BDNF) Was Measured In BAL Fluid.
6.1. The Main Findings Of The Present Investigation Can Be Summarized As Follows:
1. OVA Induced Bronchial Asthma Was Manifested By Significant Decrease Of Both TV And PEFR, Which Were Significantly Increased With DEXA Administration.
2. Allopurinol, Rosiglitazone And Fluoxetine, In The Two Dose Levels, Significantly Improved TV And PEFR As Compared To Asthma Control.
3. Intranasal OVA Challenge Significantly Increased Serum Ige Level, Which Was Significantly Decreased In DEXA Group.
4. Allopurinol, Rosiglitazone And Fluoxetine, In The Two Dose Levels Significantly Diminished Serum Ige Levels As Compared To Asthma Control.
5. OVA Challenge Significantly Increased Nox Level In BAL Fluid That Was Reduced By Administration Of DEXA.
6. Allopurinol, Rosiglitazone, In The Two Dose Levels, As Well As Fluoxetine At The Lower Dose Level Caused No Significant Alteration In Nox Level In BAL Fluid As Compared To OVA-Challenged group Rats. However, Fluoxetine At The Higher Dose Level, Significantly Suppressed BAL Fluid Nox Level As Compared To Asthmatic group Rats.
7. OVA Challenge Significantly Increased Inflammatory Cytokines As Lung Content Of TNF-Α And IL-4, Which Were Significantly Decreased By Administration Of DEXA.
8. Interestingly, Allopurinol, Rosiglitazone And Fluoxetine, In The Two Dose Levels Significantly Reduced Both TNF-Α And IL-4 Levels In Lung Tissues.
9. OVA Significantly Increased Oxidative Stress Biomarkers As Decreased Both GSH Reduced And SOD Levels And Increased MDA Level In Lung Homogenate, While DEXA Administration Significantly Enhanced GSH Reduced And SOD Levels And Decreased MDA Level.
10. Allopurinol, Rosiglitazone And Fluoxetine, In Two Dose Levels, Significantly Boosted GSH Reduced And Total SOD Levels. Additionally, Allopurinol, In The Two Dose Levels, Notably Attenuated The OVA-Induced Increase In MDA Level In Lung Homogenates.
11. Intranasal OVA Challenge Induced Severe Distortion Of Bronchial And Alveolar Architectures, With Severe Infiltration Of Inflammatory Cells. Preventive Treatment With DEXA Improved And Nearly Normalized Lung Architectures.
12. Allopurinol, Rosiglitazone And Fluoxetine, In Two Dose Levels, Improved The Lung Architecture And Reduced Peribronchiolar And Perivascular Inflammatory Cells Infiltration, Especially In Their Higher Dose Level.
13. OVA Challenge Notably Elevated BDNF Level In BAL Fluid Which Was Reduced By DEXA Pretreatment.
14. Administration Of Fluoxetine, At The Lower And The Higher Dose Level, Effectively Diminished BDNF Level In BAL Fluid. Moreover, Pretreatment With The Higher Dose Of Fluoxetine Significantly Reduced BDNF Level Approximately To The Same Extent As DEXA.
15. OVA Challenge Significantly Decreased Rearing Count And Number Of Squares Crossed In Open Field Test As Compared To Normal Control. While DEXA Showed No Significant Alteration In Rearing Count And Number Of Squares Crossed As Compared To Asthmatic Group.
16. Fluoxetine, At The Lower Dose Level, Caused No Significant Change In Rearing Count And Number Of Squares Crossed. On The Other Hand, Fluoxetine, At The Higher Dose Level, Greatly Increased Rearing Count And Number Of Squares Crossed As Compared To Asthmatic Group.
17. OVA Challenge Markedly Increased Immobility Time In Forced Swimming Test. Furthermore, DEXA Administration Caused Additional Increase In Immobility Time.
18. Fluoxetine, In The selected Two Doses, Showed Significant Reduction In Immobility Time. Furthermore, Fluoxetine (20 Mg/Kg) Nearly Prohibited The OVA-Induced Increase In Immobility Time.
6.2. from The Previous Findings, The Following Could Be Concluded:
1. Allopurinol Showed Potential Action As Bronchodilator, Anti-Inflammatory Agent And Anti-Oxidant, In Addition To Its Inhibitory Action On Ige Level.
2. Rosiglitazone Has Potential Protecting Effects Against Experimentally-Induced Bronchial Asthma In Rats Probably Due To Its Bronchodilator, Antioxidant And Anti-Inflammatory Effects.
3. Fluoxetine May Protect Against Experimentally-Induced Bronchial Asthma. This Anti-Asthmatic Effect Might Be Mediated At Least In Part By Its Antioxidant And Anti-Inflammatory Effects.
4. One Probable Implication Of This Study Is That Fluoxetine Unexpectedly Down Regulated BDNF In BAL Fluid, Probably Due To Its Anti-Inflammatory Effect. This Finding Denies The Possible Aggravating Effect Of Fluoxetine On Bronchial Asthma Symptoms.
5. The Results Of The Present Study Demonstrated That Fluoxetine Effectively Alleviated The Depressive-Like Behavior Induced By OVA Giving Advantage Over DEXA That Can Cause Further Deterioration In Depressive-Like Behavior Symptoms.
The Present Study Revealed That Drugs With Different Classes And Pharmacological Actions Can Be Used Effectively For Protection Against Bronchial Asthma. These Different Drug Classes Can Offer Similar Protective Effect As Corticosteroids With Fewer Adverse Effects.
In Conclusion, Allopurinol, Rosiglitazone And Fluoxetine Are Good Anti-Asthmatic Agents And May Be Promising For Further Clinical Trials For Prophylaxis Against Attacks Of Bronchial Asthma In Human.