ABSTRACT
The inability of an organism to efficiently remove excess waste from the body have been a major issues attached to acute kidney injury (AKI) which is the most common cause of organ dysfunction. Oleanolic acid and rutin which are from the families of saponin and flavonoid respectively have been discovered to possess certain biological activities such as anti-oxidant, anti-inflammation, anti-viral and nephroprotective activities that can help in therapeutic management of acute kidney injury. In this study, the nephroprotective effect of rutin and oleanolic acid was carried out as well as the comparative therapeutic effect of the phytochemicals on renal biomarkers and electrolytes imbalance in the serum and urine of albino rats induced with acute kidney injury. Female wistar rats (n=25) weighing 200 ± 20 g were divided into 5 groups; sham, Ischemia reperfused (I/R) group, while the remaining 3 groups were pretreated orally with a single dose of 10 mg/kg oleanolic acid, 20 mg/kg rutin and 0.143 mg/kg moduretic (Amiloride HCl and hydrochlorothiazide) respectively. Afterwards, ischemia injury was performed for 45 minutes and they were reperfused for 24 hours. Blood and urine samples were collected after reperfusion for biochemical analyses. The effect of rutin and oleanolic acid on renal biomarkers and electrolytes, albumin level and alkaline phosphatase activity were assessed in the serum and urine of the animals. The results indicated that there was a significant (p<0.05) increase in the level of all the biomarkers and most of the electrolytes as well as significant (p<0.05) decrease in the level of carbonate, albumin, and alkaline phosphatase activity in the I/R group compared with the sham. In the urine, the result showed that there was a significant (p<0.05) decrease in the level of uric acid, blood urea nitrogen, creatinine, calcium, potassium and chloride levels while the sodium level was significantly increased. Pre-treatment with oleanolic acid and rutin were able to reverse most of the effect above in the serum and the urine of the treated groups with oleanolic acid showing better therapeutic effect than rutin. The nephroprotective activity of oleanolic acid and rutin against ischemia reperfusion injury through regulation of electrolyte imbalance and renal biomarkers was affirmed with oleanolic acid exhibiting more therapeutic effect than rutin.
TABLE OF CONTENTS
| | Content | Page |
| | Title page | I |
| | Abstract | Ii |
| | Certification | Iv |
| | Dedication | V |
| | Acknowledgement | Vi |
| | Table of content | Vii |
| | List of figures | Xiii |
| | List of tables | Xiv |
| | List of plates | Xv |
| | CHAPTER ONE | |
| 1.0 | INTRODUCTION | 1 |
| 1.1 | Background | 1 |
| 1.2 | Justification | 3 |
| 1.3 | Aims and objectives | 4 |
| | CHAPTER TWO | |
| 2.0 | LITERATURE REVIEW | 5 |
| 2.1 | The kidney | 5 |
| 2.1.1 | Part of the kidney and their function | 6 |
| 2.1.2 | General function of the kidney | 7 |
| 2.1.3 | Kidney biomarkers and renal function tests | 8 |
| 2.1.4 | Ischemia reperfusion injury | 11 |
| 2.1.5 | Nephroischemia and effect on the body system | 14 |
| 2.1.6 | Recent research on the use of medicinal plants in the treatment of nephroischemia | 15 |
| 2.2 | Phytochemicals | 17 |
| 2.2.1 | Saponin | 18 |
| 2.2.1.1 | Classes of saponins | 19 |
| 2.2.1.2 | Sources of saponin | 21 |
| 2.2.2 | Oleanolic acid | 23 |
| 2.2.2.1 | Pharmacological activities of olealonic acid | 23 |
| 2.2.2.1.1 | Cytochrome p450 enzyme inhibition activity | 23 |
| 2.2.2.1.2 | Anti-inflammatory activity | 23 |
| 2.2.2.1.3 | Anti-cancer activity | 24 |
| 2.2.2.1.4 | Anti-fertility activity | 24 |
| 2.2.2.1.5 | Anti-hyperlipidaemia activity | 24 |
| 2.2.2.1.6 | Hypoglycaemic and antidiabetic activity | 25 |
| 2.2.2.1.7 | Hepatoprotective activity | 25 |
| 2.2.3 | Flavonoids | 26 |
| 2.2.3.1 | Sources of flavonoids | 27 |
| 2.2.3.2 | Classes of flavonoids | 28 |
| 2.2.3.3 | Therapeutic use of flavonoids | 29 |
| 2.2.4 | Rutin | 31 |
| 2.2.4.1 | Pharmacological activities of rutin | 31 |
| 2.2.4.1.1 | Hepatoprotective activity | 32 |
| 2.2.4.1.2 | Anti-hypercholesterolamic activity | 32 |
| 2.2.4.1.3 | Nephroprotective activity | 33 |
| 2.2.4.1.4 | Antidiabetic activity | 34 |
| 2.2.4.1.5 | Cardioprotective activity | 35 |
| 2.2.4.1.6 | Antibacterial activity | 36 |
| 2.2.4.1.7 | Antifungal activity | 37 |
| 2.2.4.1.8 | Antiviral activity | 37 |
| 2.2.4.1.9 | Antiarthritic activity | 37 |
| 2.3 | Oxidative stress | 38 |
| 2.3.1 | Free radical formation in the body systems | 39 |
| 2.3.2 | Antioxidants role in scavenging free radical | 41 |
| | CHAPTER THREE | |
| 3.0 | MATERIAL AND METHODS | 44 |
| 3.1 | Materials | 44 |
| 3.1.1 | Chemicals and reagents | 44 |
| 3.1.2 | Animals | 44 |
| 3.2 | Methods |
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