الفهرس 
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Abstract
In The Present Study, The Possible Protective Anti-Diabetic Effects Of Resveratrol And Simvastatin Besides Their Influence On CXCL16/Ox-LDL-Induced Autophagy, TF Activation In Pancreatic Islets, In Addition To Their Action On Macrophage Activation Via Pancreatic Infiltration Or Splenic Migration In Streptozotocin (STZ)-Induced Type 1 Diabetes Mellitus Model In Adult Male Albino Mice Were Studied. The Test Drugs Were Given For Normal As Well As STZ -Treated Mice For 12 Consecutive Days Starting from The Fourth Day Of STZ Or Buffer Injection. T1DM Was Induced Through STZ Injection Of Dose 55 Mg/Kg, I.P. For 5 Consecutive Days. The Degree Of T1DM And Metabolic Disturbance Was Assessed By Measuring Physical And Biochemical Tests Such As Body Weight, 24hr Diuresis, Random And Fasting Blood Glucose, Serum Insulin, Glucose Tolerance, Food And Water Consumption As Well As Lipid Profile. Furthermore, Serum Malondialdehyde (MDA) And Blood Glutathione (GSH) Content Were Measured As Oxidative Stress Biomarkers. Histopathological Study Was Performed To Confirm Biochemical Findings.
In Addition, Immunofluorescence Analysis Was Done To Determine The Effect Of STZ And Test Drugs On CXCL16, Ox-LDL, TF, CD45 Expression Levels In Pancreatic Beta Cells. Furthermore, CD45 And CXCL16 Protein Expression Was Assessed In Spleen. Additionally, Western Blotting Analysis Was Performed To Investigate The Effect Of STZ And Test Drugs On CXCL16, Ox-LDL, TF, NF-KB P65, P62 And LC3 Expression Levels In Isolated Pancreatic Islets.
The Main Findings Of The Present Study Can Be Summarized As Follows:
1. Resveratrol And Simvastatin, As Single Treatments, Did Not Significantly Affect Body Weight, 24hr Diuresis, Random And Fasting Blood Glucose, Serum Insulin, Glucose Tolerance, Food And Water Consumption As Well As Lipid Profile In Normal Animals.
2. Streptozotocin (STZ) Caused A Significant Loss In Body Weight, Increase In 24hr Diuresis, Random And Fasting Blood Glucose, Glucose Intolerance, Food And Water Consumption As Well As Lipid Profile Accompanied By A Significant Decrease In Serum Insulin.
3. Resveratrol And Simvastatin Significantly Ameliorated STZ-Induced Body Weight Loss, Glucose Intolerance, Elevation In 24hr Diuresis, Random And Fasting Blood Glucose, Food And Water Consumption As Well As Lipid Profile As Well As Decreased Serum Insulin.
4. Resveratrol And Simvastatin, As Single Treatments, Did Not Significantly Affect Serum MDA, Blood GSH, Serum Ox-LDL, Platelets And White Blood Cells (Wbcs) Count In Normal Animals.
5. STZ Significantly Elevated Serum MDA, Serum Ox-LDL, Platelets And Wbcs Count While Significantly Blood GSH.
6. Resveratrol And Simvastatin Have Significantly Reduced STZ -Induced Elevation Of Serum MDA, Serum Ox-LDL, Platelets And Wbcs Count While Significantly Increased STZ -Induced Reduction Of Blood GSH.
7. Histopathological Examination Of Pancreatic Tissue Of Mice Treated With Resveratrol And Simvastatin, As Single Treatments, Did Not Show Any Significant Disruption Of The Normal Pancreas Architecture.
8. Histopathological Examination Of Groups Treated With STZ Showed Markedly Distorted Architecture With Small-Sized Hypo-Cellular Islet, Notable Atrophy Of Beta Cells, Degenerative Changes, Scattered Apoptotic Beta Cells And Average Exocrine Areas.
9. Histopathological Examination Of STZ Groups Treated With Resveratrol Or Simvastatin Showed Very Mild Alterations Less Than Those Showed In STZ group Indicating That They Began To Restore The Normal Architecture Of Pancreas Tissues.
10. Immunofluorescence Analysis Of Pancreatic Tissue Of Mice Treated With Resveratrol Or Simvastatin, As Single Treatments, Showed That They Did Not Significantly Affect The Expression Level Of CXCL16, Ox-LDL, TF, CD45 In Pancreatic Beta Cells In Normal Groups.
11. Immunofluorescence Analysis Of Pancreatic Tissue Of Mice Treated With STZ Showed A Significant Increase In The Expression Level Of CXCL16, Ox-LDL, TF, CD45 In Pancreatic Beta Cells While Showed A Significant Decrease Of CXCL16 And CD45 In Spleen As Compared To Normal Group.
12. Immunofluorescence Analysis Of Pancreatic Tissue Of Mice Treated With Resveratrol And Simvastatin Showed Significant Decrease In STZ -Induced Elevation In Expression Level Of CXCL16, Ox-LDL, TF, CD45 In Pancreatic Beta Cells While Restored The Expression Of CXCL16 And CD45 In Spleen.
13. Western Blot Analysis Of Isolated Pancreatic Islets from Mice Treated With STZ Showed A Significant Increase In The Expression Level Of CXCL16, Ox-LDL, TF, NF-KB P65, P62 And LC3 As Compared To Normal Group.
14. Western Blot Analysis Of Isolated Pancreatic Islets from Mice Treated With Resveratrol And Simvastatin Showed Significant Decrease In STZ -Induced Elevation In Expression Level Of CXCL16, Ox-LDL, TF, NF-KB P65, P62 And LC3.
from The Previous Findings, It Could Be Concluded That:
1. Resveratrol And Simvastatin Possess No Toxic Effects On Pancreas Of Normal Mice.
2. Streptozotocin (STZ) Induced Type 1 Diabetes Mellitus (T1DM) In Mice, Which Was Evidenced By Significant Metabolic Disturbance, Obvious Oxidative Stress Status And Lipid Profile Deterioration.
3. Targeting Ox-LDL And CXCL16 Might Offer A New Attractive Strategy To Prevent Pancreatic Islets Autophagy-Induced Β-Cell Death, Coagulation-Mediated TF Activation And CXCL16-Driven Macrophage Recruitment In T1DM.
4. Resveratrol Or Simvastatin Improved T1DM Not Only Through Modulation Of Redox Status And Attenuation Of The Metabolic Disturbance But Also In Part, Through Mitigation Of Ox-LDL-Induced Autophagic Β-Cell Death, Pancreatic TF Activation And CXCL16-Driven Macrophage Recruitment.
5. Resveratrol Or Simvastatin Could Be Promising For Clinical Use As Adjuvant Anti-Diabetic Agents For Prevention Against T1DM. Further Clinical Studies Are Required To Prove Present Findings.
This Study Gives The First Direct Evidence That Pancreatic Islets Autophagy-Induced Β-Cell Death, Coagulation-Mediated TF Activation And CXCL16-Driven Macrophage Recruitment May Be Potential Triggers Of T1DM Initiation And Development. Moreover, Resveratrol And Simvastatin May Have Potential Therapeutic Applications For Prevention Of T1DM Mainly Via Ameliorating These Pathways.