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Myocardial Infarction in Irradiated Rats

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Myocardial Infarction in Irradiated Rats BIOCHEMICAL STUDY ON THE PROTECTIVE EFFECT OF ANTIOXIDANT AND β-ADRENERGIC BLOCKING AGENT AGAINST EXPERIMENTAL MYOCARDIAL INFARCTION IN IRRADIATED RATS Ph.D. Presented by Hanan Fahmy Abdel-Hamied Assistant lecturer Drug Radiation Research Department National Center for Radiation Research and Technology (NCRRT) Atomic Energy Authority For the Degree OF Doctor of Philosophy in Pharmaceutical sciences (Biochemistry) Under The Supervision of Prof. Dr Ola Sayed M. Ali Prof. Dr. Seham Hassan Mohamed Professor of Biochemistry Professor of Vice Dean of Pharmacology&Toxicology Faculty of Pharmacy (Girls) Vice Chairman of the Biotechnology Al-Azhar University Sector (NCRRT) Atomic Energy Authority Dr. Ragia Ali Taha Assistant Professor of Pharmacology Faculty of pharmacy (Girls) AL-Azhar University Faculty of Pharmacy (Girls) Al- Azhar University (2009) ACKNOWLEDGMENT First and foremost thanks to Allah, the most merciful for guiding and giving me the strength to complete this work. My sincere thanks and gratitude to Prof. Dr. Ola Sayed , Vice Dean & prof. of Biochemistry, faculty of pharmacy (Girls), A- Azhar University for her keen supervision, valuable advice, great support and sincere help throughout this thesis. My cordial thanks and appreciation are given to Prof. Dr. Seham Hassan vice chairman of biotechnology sector & Prof. of Pharmacology & Toxicology, (NCRRT), Atomic Energy Authority, Cairo, for suggesting the point, keen supervision, expert advice and for her help in carrying out experimental investigation, writing, reviewing the thesis and for her kind help to overcome many of the difficulties that arose in the course of this research. I am also grateful to Dr. Ragia Taha Assistant Prof. of pharmacology, faculty of pharmacy (Girls), Al- Azhar University .for her kind supervision, encouragement and support throughout revising this thesis. Also, I would like to express my thanks to Dr. Seham Abo-Nour , Prof. of histology, Radiation Health Research Department (NCRRT) for her participation in the histopathological part of the research. I would like to express my thanks to Dr. Ahmed Shafik Nada, Assistant Prof of physiology, Radiation Drug Research Department, (NCRRT) for helping in the Atomic Absorption Ions Spectroscopy measurements. My deepest thanks extend to Dr Abdu Mansour lecturer of physics & a member in the Electron Spin Resonance (ESR) Lab, Central Laboratories, (NCRRT) for helping in ESR analysis. A special word of thankfulness is directed to Dr Hala Farag Prof of microbiology & head of Drug Research and Technology Department (NCRRT) for her helpful advice and encouragement. I would like also to give my thanks and appreciation to all members of the Department of Drug Research and Technology for their constant help and encouragement. I would like to give my appreciation to the staff member of gamma irradiation unit for unforgettable cooperation in carrying out experimental irradiation. Finally no thanks can repay my husband, my parents and my brothers for their continuous help, support and to my children for their patience which enable this work to be completed. List of Contents Aim of The Work 1 Introduction 2 Ionizing Radiations 2 Radiation Types 2 Interaction of radiation with matter 4 Units of Ionizing Radiation 6 Biological Effects of Ionizing Radiation: 8 Free Radicals and Human Diseases 14 Myocardial Infarction 15 Isoproterenol 19 Adrenoreceptor blocking drugs 22 Carvedilol. 24 Antioxidant 26 Taurine 27 Material and Methods 30 A-Material 30 B-Experimental Design 32 Methods 34 A-Blood Sampling 34 B-Tissue Sampling 34 Ι- Assessment OF (HW/BW) ratio 35 П- Assessment of Lipid Profile Pattern 35 A-Determination of Serum Total Cholesterol 35 B-Determination of Serum Triglyceride 37 C-Determination of Serum HDL-Cholesterol 38 D –Estimation of Serum LDL-Cholesterol 40 E–Estimation of Serum VLDL 40 F-Estimation of Serum Risk Factor And Athrogenic Index 40 ПΙ - Cardiac Enzymes Assay 40 A-Determination of Serum (GOT) Activity 40 B-Determination of Serum (LDH) 42 C-Determination of Serum CK-MB) 43 D-Determination of Troponin 44 IV-Determination of Total Blood Free Radicals 44 V-Determination of Calcium and Magnesium 49 VI- Evaluation of DNA Fragmentation 49 Statistical Analysis 51 Results 52 DISCUSSION 115 SUMMARY & CONCLUSION 133 REFERENCES 138 List of Tables Table 1: Effect of Gamma Irradiation (5Gy) or Isoproterenol (85mg/kg) Induced Myocardial Infarction on (HW/BW) ratio of Male Rats. 53 Table 2: Effect of Fractionated Gamma Irradiation (5x2Gy) or Isoproterenol (85mg/kg) Induced Myocardial Infarction on HW/BW ratio of Male Rats. 53 Table 3: Effect of Carvedilol (30mg/Kg) on weight ratio(HW/BW) of Irradiated (5Gy) Male Rats with Isoproterenol (85mg/Kg) Induced Myocardial Infarction. 56 Table 4: Effect of Carvedilol (30mg/Kg) on weight ratio (HW/BW) of Irradiated (5x2Gy) Male Rats with Isoproterenol (85mg/Kg) Induced Myocardial Infarction. 56 Table 5: Effect of Taurine (1.1g/Kg) on weight Ratio (HW/BW) of Irradiated (5Gy) Male Rats with Isoproterenol (85mg/Kg) Induced Myocardial Infarction. 59 Table 6: Effect of Taurine (1.1g/Kg) on weight ratio (HW/BW) of Irradiated (5x2Gy)Male Rats with Isoproterenol (85mg/Kg) Induced Myocardial Infarction. 59 Table 7: Effect of Gamma Irradiation (5Gy) or Isoproterenol (85mg/kg) Induced Myocardial Infarction on Serum Cholesterol and Triglyceride levels of Male Rats. 62 Table 8: Effect of Fractionated Gamma Irradiation (5x2Gy) or Isoproterenol (85mg/kg) Induced Myocardial Infarction on Serum Cholesterol and Triglyceride levels of Male Rats. 62 Table 9: Effect of Carvedilol (30mg/Kg) on Serum Cholesterol and Triglyceride Levels of Irradiated (5Gy) Male Rats with Isoproterenol (85mg/Kg)-Induced Myocardial Infarction. 65 Table 10: Effect of Carvedilol (30mg/Kg) on Serum Cholesterol and Triglyceride Levels of Irradiated (5x2Gy) Male Rats with Isoproterenol (85mg/Kg)-Induced Myocardial Infarction. 65 Table 11: Effect of Taurine (1.1g/Kg) on Serum Cholesterol and Triglyceride Levels of Irradiated (5Gy) Male Rats with Isoproterenol (85mg/Kg)-Induced Myocardial Infarction. 68 Table 12: Effect of Taurine (1.1g/Kg) on Serum Cholesterol and Triglyceride Levels of Irradiated (5x2Gy) Male Rats with Isoproterenol (85mg/Kg) Induced Myocardial Infarction. 68 Table 13: Effect of Gamma Irradiation (5Gy) or Isoproterenol (85mg/kg)- Induced Myocardial Infarction on Serum Lipoprotein Levels of Male Rats. 71 Table 14: Effect of Fractionated Gamma Irradiation (5x2Gy) or Isoproterenol (85mg/kg) Induced Myocardial Infarction on Serum Lipoprotein Levels of Male Rats. 71 Table 15: Effect of Carvedilol (30mg/Kg) on Serum Lipoprotein Levels of Irradiated (5Gy) Male Rats with Isoproterenol (85mg/Kg)-Induced Myocardial Infarction. 74 Table 16: Effect of Carvedilol (30mg/Kg) on Lipoprotein Levels of Irradiated (5x2Gy) Male Rats with Isoproterenol (85mg/Kg) Induced Myocardial Infarction. 74 Table 17: Effect of Taurine (1.1g/Kg) on Serum Lipoprotein Levels of Irradiated (5Gy) Male Rats with Isoproterenol (85mg/Kg)-Induced Myocardial Infarction. 77 Table 18: Effect of Taurine (1.1g/Kg) on Serum Lipoprotein levels of Irradiated (5x2Gy) Male Rats with Isoproterenol (85mg/Kg)-Induced Myocardial Infarction. 77 Table 19: Effect of Gamma Irradiation (5Gy) or Isoproterenol (85mg/kg) Induced Myocardial Infarction on Serum Biomarker Levels of Male Rats. 80 Table 20: Effect of Fractionated Gamma Irradiation (5x2Gy) or Isoproterenol (85mg/kg) Induced Myocardial Infarction on Serum Cardiac Biomarker Levels of Male Rats. 80 Table 21: Effect of Carvedilol (30mg/Kg) on Serum Cardiac Biomarker Levels of Irradiated(5Gy) Male Rats with Isoproterenol Induced Myocardial Infarction. 83 Table 22: Effect of Carvedilol (30mg/Kg) on Serum Cardiac Biomarker Levels of Irradiated (5x2Gy) Male Rats with Isoproterenol Induced Myocardial Infarction. 83 Table 23: Effect of Carvedilol (30mg/Kg) on Serum Cardiac Biomarker Levels of Irradiated(5Gy) Male Rats with Isoproterenol Induced Myocardial Infarction. 86 Table 24: Effect of Carvedilol (30mg/Kg) on Serum Cardiac Biomarker Levels of Irradiated (5x2Gy) Male Rats with Isoproterenol Induced Myocardial Infarction. 86 Table 25: Effect of Gamma Irradiation (5Gy) or Isoproterenol (85mg/kg) Induced Myocardial Infarction on Blood Total Free Radicals Concentration (Radical /gx1017) of Male Rats. 89 Table 26: Effect of Fractionated Gamma Irradiation (5x2Gy) or Isoproterenol (85mg/kg)-Induced Myocardial Infarction on Total Blood Free Radicals Concentration (Radical/g x1017) of Male Rats. 89 Table 27: Effect of Carvedilol (30mg/Kg) on Blood Total Free Radicals Concentration (Radical/g x1017) of Irradiated (5Gy) Male Rats with Isoproterenol (85mg/Kg)-Induced Myocardial Infarction. 92 Table 28: Effect of Carvedilol (30mg/Kg) on Blood Total Free Radicals Concentration (Radical/gx1017) of Irradiated Male Rats (5x2Gy) with Isoproterenol (85mg/Kg)-Induced Myocardial Infarction. 92 Table 29: Effect of Taurine (1.1g/Kg) on Blood Total Free Radicals Concentration (Radical/gx1017) of Irradiated (5Gy) Male Rats with Isoproterenol (85mg/Kg)-Induced Myocardial Infarction. 95 Table 30: Effect of Taurine (1.1g/Kg) on Blood Total Free Radicals Concentration (Radical/g x1017) of Irradiated (5x2Gy) Male Rats with Isoproterenol (85mg/Kg)-Induced Myocardial Infarction. 95 Table 31: Effect of Gamma Irradiation (5Gy) or Isoproterenol (85mg/kg) Induced Myocardial Infarction on Heart Calcium and Magnesium Concentrations of Irradiated Male Rats. 98 Table 32: Effect of Fractionated Gamma Irradiation (5x2Gy) or Isoproterenol (85mg/kg)
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