Effects of Thiamine, Pyridoxine and Biotin on Blood Glucose Concentration and Renal Function Parameters of Alloxan-Induced Diabetic Rats

Effects of Thiamine, Pyridoxine and Biotin on Blood Glucose Concentration and Renal Function Parameters of Alloxan-Induced Diabetic Rats.

ABSTRACT

The aim of this study was to investigate the effects of thiamine, pyridoxine and biotin on the concentrations of blood glucose, serum electrolytes and renal functions of alloxan-induced diabetic rats. A total of twenty seven (27) adult male albino rats of Wistar strain weighing between 160-200 g were used for the study.

Twenty four (24) of the animals were rendered diabetic by a single and freshly prepared alloxan monohydrate dissolved in 0.9% ice cold normal saline solution and injected intraperitoneally at a dose of 100 mg/kg body weight. Forty eight (48) hours after confirmation of experimental diabetes, the rats were randomly divided into nine (9) experimental groups of three (3) rats each.

Group 1 served as the normal control while Group 2 served as the diabetic control (diabetic untreated). In group 3 (standard control), metformin was used as a reference standard drug at a dose of 100 mg/kg body weight. Group 4 (diabetic rats treated with 25 mg/kg body weight of thiamine), Group 5 (diabetic rats treated with 25 mg/kg body weight of pyridoxine), Group 6 (diabetic rats treated with 0.5 mg/kg body weight of biotin).

Group 7 (diabetic rats treated with 100 mg/kg of metformin and 25 mg/kg of thiamine), Group 8 (diabetic rats treated with 100 mg/kg of metformin and 25 mg/kg of pyridoxine) and Group 9 (diabetic rats treated with 100 mg/kg of metformin and 0.5 mg/kg of biotin). Blood glucose concentrations, serum electrolytes and renal function parameters were analysed.

The results obtained showed that oral administration of thiamine, pyridoxine and biotin, after the seventh day of treatment significantly (p < 0.05) lowered blood glucose concentrations when compared to the values obtained for Group 2 (untreated) rats. Co-administration of thiamine and biotin with the metformin however, was observed to be more efficacious as they significantly lowered blood glucose concentration when compared to the values obtained for groups 2, 4 and 6.

TABLE OF CONTENTS

Title Page i

Certification ii

Dedication iii

Acknowledgments iv

Abstract v

Table of Contents vi-ix

List of Figures x

List of Tables xi

List of Abbreviations xii

CHAPTER ONE: INTRODUCTION

1.1 Thiamine (Vitamin B1) 3

1.1.1 Coenzyme Functions 3

1.1.2 Thiamine Deficiency 5

1.1.3 Disease Prevention and Treatment 6

1.1.4 Sources and Supplements of Thiamine 6

1.1.5 The Recommended Dietary Allowance 7

1.2 Pyridoxine (Vitamin B6) 7

1.2.1 Biosynthesis of Pyridoxal 5-Phosphate 8

1.2.2 Coenzyme Functions of Vitamin B6 9

1.2.3 Deficiency of Vitamin B6 13

1.2.4 Medical Applications of Vitamin B6 13

1.2.5 Sources and Supplement of Vitamin B6 14

1.2.6 Recommended Dietary Allowance 14

1.3 Biotin (Vitamin B7) 14

1.3.1 Biosynthesis of Biotin 15

1.3.2 Roles of Biotin 15

1.3.3 Biotin Deficiency 22

1.3.4 Disease Prevention and Treatment 22

1.3.4.1 Role of Biotin in the Treatment of Diabetes mellitus 22

1.3.5 Sources and Supplement of Biotin 23

1.3.6 The Adequate Intake 24 vii

1.4 Diabetes Mellitus 24

1.4.1 Type 1 Diabetes Mellitus 24

1.4.2 Type 2 Diabetes Mellitus 25

1.4.3 Gestational Diabetes 25

1.5 Clinical Features and Diagnosis of Diabetes Mellitus 25

1.6 Prevention and Management of Diabetes Mellitus 26

1.7 Thiamine, Pyridoxine and Biotin in Diabetes Mellitus 26

1.8 Experimental Animal Models of Diabetes 28

1.8.1 Alloxan 28

1.8.2 Phases of Diabetes Induction 29

1.8.3 Mechanism of Action of Alloxan 30

1.8.4 Biological Effects 32

1.9 Metformin 33

1.9.1 Mechanism of Action 34

1.10 Blood Glucose Concentration 34

1.11 Electrolytes 35

1.11.1 Sodium 36

1.11.2 Potassium 36

1.11.3 Chloride 37

1.11.4 Bicarbonate 37

1.12 Renal Function 38

1.12.1 Urea/Blood Urea Nitrogen 38

1.12.2 Uric Acid 39

1.12.3 Creatinine 39

1.13 Rationale of the Study 40

1.14 Aim of the Study 41

1.12.1 Specific Objectives of the Study 41

CHAPTER TWO: MATERIALS AND METHODS

2.1 Materials 42

2.1.1 Equipment/Apparatus 42

2.1.2 Chemicals and Reagents 42

2.1.3 Drugs 42

2.1.4 Experimental Animals

2.2 Methods 43

2.2.1 Experimental Design 43

2.2.2 Induction of Experimental Diabetes 44

2.2.3 Collection of Blood Samples and Preparation of Sera for Analyses 44

2.2.4 Determination of Blood Glucose Concentration 44

2.2.5 Determination of Some Serum Electrolyte Concentration 45

2.2.5.1 Determination of Serum Sodium Concentration 45

2.2.5.2 Determination of Serum Potassium Concentration 46

2.2.5.3 Determination of Serum Chloride Concentration 47

2.2.5.4 Determination of Serum Bicarbonate Concentration 48

2.2.6 Renal Function Tests 49

2.2.6.1 Determination of Serum Urea Concentration 49

2.2.6.2 Determination of Blood Urea Nitrogen (BUN) 49

2.2.6.3 Determination of Serum Uric Acid Concentration 50

2.2.6.4 Determination of Serum Creatinine Concentration 50

2.2.7 Statistical Analysis 51

CHAPTER THREE: RESULTS

3.1 Effect of thiamine, pyridoxine and biotin on blood glucose concentrations of alloxan-induced diabetic rats 52

3.2 Effect of thiamine on sodium, potassium, chloride and bicarbonate ion concentrations of alloxan-induced diabetic rats 54

3.3 Effect of pyridoxine on sodium, potassium, chloride and bicarbonate ion concentrations of alloxan-induced diabetic rats 56

3.4 Effect of biotin on sodium, potassium, chloride and bicarbonate ion concentrations of alloxan-induced diabetic rats 58

3.5 Effect of thiamine on urea, blood urea nitrogen, uric acid and creatinine concentrations of alloxan-induced diabetic Rats 60

3.6 Effect of pyridoxine on urea, blood urea nitrogen, uric acid and creatinine concentrations of alloxan-induced diabetic rats 62

3.7 Effect of biotin on urea, blood urea nitrogen, uric acid and creatinine concentrations of alloxan-induced diabetic rats 64

CHAPTER FOUR: DISCUSSION

4.1 Discussion 66

4.2 Conclusion 72

4.3 Suggestion for Further Studies 72

References 73

Appendix 91

INTRODUCTION

Diabetes mellitus, commonly referred to as diabetes, is a metabolic disorder characterized by high blood sugar (glucose) levels over a prolonged period of time and results from defects in insulin secretion, or its action, or both (Kitabchi et al., 2009). Normally, blood glucose levels are tightly controlled by insulin, a hormone produced by the beta cells of the pancreas.

Insulin is a water soluble hormone whose receptor is a tyrosine kinase (Rang et al., 2012). It functions primarily to lower blood glucose level by providing a mechanism for the uptake and utilization of glucose. When the blood glucose elevates (for example after a carbohydrate rich meal), insulin is secreted from the pancreas to normalize the blood glucose level.

The inability of the pancreas to produce sufficient insulin or the cells of the body to respond to the insulin produced results in a state of hyperglycaemia and subsequently causes diabetes (David and Dolores, 2011). The prevalence of diabetes for all age groups worldwide was estimated to be 2.8% in 2000 and 4.4% by 2030. The total number of people with diabetes is projected to rise from 171 million in 2000 to 366 million in 2030 (Wild et al., 2003).

Vitamins are organic compounds occurring in small quantities in different natural foods necessary for growth and maintenance of good health in humans and animals. They cannot be synthesized by the body, hence are required in diets and food supplements in other to maintain adequate amounts. They are classified as fat soluble and water soluble vitamins.

All water soluble B vitamins help the body to convert food (carbohydrates) into fuel (glucose), which is used to produce energy (Vasudevan and Sreekumari, 2007). Thiamine (Vitamin B1), pyridoxine (vitamin B6) and biotin (vitamin B7) are part of the B complex group of vitamins. These B vitamins, often referred to as B complex vitamins, also help the body metabolize fats and protein.

REFERENCES

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Afolayan, A.J. and Yakubu, M.T. (2009). Effect of Bulbine natalenis baker stem extract on the functional indices and histology of the liver and kidney of male Wistar rats. Journal of Medicinal Food, 12: 814-820.
Ahn, H.J., Min, K.W. and Cho, Y.O. (2011). Assessment of vitamin B6 status in Korean patients with newly diagnosed type 2 diabetes. Nutrition Research and Practise, 5(1): 34-39.
Alaei, S.F., Soares, M.J., Zhao, Y. and Sherriff, J. (2013). High-dose thiamine supplementation improves glucose tolerance in hyperglycaemic individuals: A randomized, double-blind cross-over trial. European Journal of Clinical Nutrition, 52 (7): 1821-1824

CSN Team.

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