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Nephroprotective and Hepatoprotective Effects

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Nephroprotective and Hepatoprotective Effects NEPHROPROTECTIVE AND HEPATOPROTECTIVE EFFECTS OF TERMINALIA IVORENSIS A. CHEV. ETHANOLIC STEM BARK EXTRACT ON SPRAGUE DAWLEY RATS A THESIS SUBMITTED IN FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF PHILOSOPHY In the Department of Pharmacology Faculty of Pharmacy and Pharmaceutical Sciences By MOOMIN ALIU KWAME NKRUMAH UNIVERSITY OF SCIENCE & TECHNOLOGY, KUMASI OCTOBER, 2015 DECLARATION The experimental work described in this thesis was carried out at the Department of Pharmacology, KNUST. This work has not been presented for any other degree. ………………………….. ………………………….. Moomin Aliu Date (Student) …………………………… …………………………….. Rev. Prof. Charles Ansah Date (Supervisor) ii DEDICATION I dedicate this work to my family. iii ABSTRACT Terminalia ivorensis has been West African ethnomedicine for the management of several diseases. For instance, to treat ulcers, wounds, general body pains, hemorrhoids, diuresis, malaria and yellow fever. In this study, T. ivorensis was assessed for potential nephroprotective and hepatoprotective actions using potassium dichromate and gentamycin as nephrotoxicant and hepatotoxicant respectively in Sprague Dawley rats. The extract (100 – 5000 mg/kg) administered to the rats for 24 hours in an acute toxicity study did not show undesirable effects on the general behavior of rats and no death was recorded. The LD50 was estimated to be above 5000 mg/kg of extract. In the nephroprotective study, administration of potassium dichromate (20 mg/kg; sc) caused elevation of creatinine from the control value of 27.83 μmL/L to 358.70 μmL/L. Urea levels also increased from 5.09 mmol/L to 56.55 mmol/L. Administration of the T. ivorensis extract with the nephrotoxicant reduced the elevated creatinine to 123.70 μmL/L and urea to 27.81 mmol/L at the highest dose of 1000 mg/kg of the extract. The reduced levels of endogenous antioxidants observed with potassium dichromate treatment, was also significantly reversed by T. ivorensis extract. Similar results were obtained with gentamycin as the nephrotoxicant. In the hepatoprotective investigations using gentamycin as hepatotoxicant, T. ivorensis the elevated levels of AST, ALT and GGT from 985.5 U/L to 361.2 U/L, 218.8 U/L to 126.2 U/L and 4.6 U/L to 2.0 U/L respectively. The Histopathological studies confirmed that T. ivorensis extract is nephroprotective and hepatoprotective in rats by a mechanism possibly related to the antioxidant effect of the extract. iv ACKNOWLEDGEMENTS I give thanks and glory to the Almighty God for his gift of life and purpose. My sincere gratitude goes to my supervisor, Rev. Prof. Charles Ansah for his criticisms, support and mentorship which helped me to the successful completion of this project. I thank all senior members of the Department of Pharmacology, KNUST, especially Dr. David D. Obiri, Dr. Kwesi Boadu Mensah, Dr. Eric Boakye Gyasi, Dr. W.K.M. Abotsi and Mr. Michael B. Adinortey (UCC) for their encouragement, direction and support. I express special thanks to Alhaj Moomin Hassan and family, Alhaj Mahama Iddrisu and Alhaj Issah Saeed for their advices and financial support offered me to pursue this degree. I am also grateful to the technicians of the Department of Pharmacology and Central lab especially Mr. Thomas Ansah, Dr. Edmund Ekuadze, Edmund Dery, Gordon Darku, Prince and Prosper as well as Mr. Asare Osafo Clifford (Herbal Medicine), Yeboah (KATH, Biochemistry lab) and Clement (KATH, Histology lab). To all my postgraduate colleagues: Charles Benneh, Asare Fredrick, Paa Kofi, Aaron Antwi, Arnold, Newmann and Biney for their encouragement and support which motivated me in times of distress, I say thank you. THANK YOU ALL. v TABLE OF CONTENTS DECLARATION ................................................................................................................... II DEDICATION ...................................................................................................................... III ABSTRACT ........................................................................................................................... IV ACKNOWLEDGEMENTS ..................................................................................................V TABLE OF CONTENTS ..................................................................................................... VI LIST OF FIGURES ............................................................................................................ XII LIST OF TABLES ............................................................................................................. XIV LIST OF ABBREVIATIONS ............................................................................................XV CHAPTER ONE INTRODUCTION ................................................................................... 1 1.1 OVERVIEW ................................................................................................................. 1 1.2 THE PLANT: TERMINALIA IVORENSIS ............................................................... 3 1.2.1 Taxonomy ............................................................................................................ 4 1.2.2 Geographical distribution .................................................................................... 5 1.2.3 Traditional Uses ................................................................................................... 5 1.2.4 Previous works on T. ivorensis ........................................................................... 6 1.3 THE KIDNEY .............................................................................................................. 7 1.3.1 Structure of the kidney ......................................................................................... 7 1.3.2 Functions of the kidney...................................................................................... 10 1.3.3 Toxicity to the kidney ........................................................................................ 11 1.3.3.1 Pathogenic Mechanisms of toxicity .............................................................. 12 vi 1.3.4 Assessment of kidney function .......................................................................... 13 1.3.4.1 Blood Urea Nitrogen (BUN) ......................................................................... 14 1.3.4.2 Creatinine levels ............................................................................................ 15 1.4 THE LIVER ................................................................................................................ 16 1.4.1 Structure of the liver .......................................................................................... 16 1.4.2 Functions of the liver ......................................................................................... 18 1.4.3 Toxicity to the liver ............................................................................................ 19 1.4.3.1 Mechanism of hepatotoxicity ........................................................................ 19 1.4.4 Assessment of liver function ............................................................................. 20 1.5 BIOMARKERS FOR ASSESSING CELLULAR INJURY .................................... 21 1.5.1 Reduced glutathione .......................................................................................... 22 1.5.2 Superoxide dismutase (SOD) ............................................................................ 23 1.5.3 Catalase .............................................................................................................. 24 1.5.4 Lipid peroxidation .............................................................................................. 24 1.5.5 Myeloperoxidase (MPO) ................................................................................... 25 1.6 JUSTIFICATION FOR THE PRESENT STUDY .................................................... 26 1.7 AIM AND SPECIFIC OBJECTIVES ....................................................................... 28 1.7.1 Aim: .................................................................................................................... 28 1.7.2 Specific objectives of the study; ........................................................................ 28 CHAPTER TWO MATERIALS AND METHODS ........................................................ 30 2.1 PREPARATION OF PLANT MATERIAL .............................................................. 30 2.2 ANIMALS .................................................................................................................. 31 2.3 CHEMICALS AND DRUGS .................................................................................... 31 vii 2.4 PHYTOCHEMICAL ANALYSES ........................................................................... 31 2.4.1 Test for flavonoids ............................................................................................. 32 2.4.2 Test for alkaloids ................................................................................................ 32 2.4.3 Test for steroids .................................................................................................. 32 2.4.4 Test for tannins ................................................................................................... 32 2.4.5 Test for saponins ................................................................................................ 32 2.4.6 Test for terpenoids ............................................................................................
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