AMELIORATIVE EFFECT OF SELENIUM YEAST ON SOME PHYSIOLOGICAL PARAMETERS IN STREPTOZOTOCIN-INDUCED DIABETIC WISTAR RATS


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TABLE OF CONTENTS

Title page
Abstract
Table of contents
List of abbreviation

CHAPTER ONE
1.0       INTRODUCTION
1.1       Background of the study
1.2       Statement of research problem
1.3       Justification of the study
1.4       Hypothesis
1.5       Aim of the study
1.5.1 Objective of the study

CHAPTER TWO
2.0 LITERATURE REVIEW
2.1       Blood glucose homeostasis
2.2       Diabetes mellitus
2.2.1 Type 1 diabetes
2.2.2 Type 2 diabetes
2.2.3 Type 3 Maturity onset diabetes of the Young (Mody)
2.2.4 Type 4 diabetes mellitus (Gestational diabetes)
2.2.5 Neonatal diabetes
2.2.6 Idiopathic diabetes mellitus
2.3       Insulin
2.3.1 Insulin receptor
2.3.2 Function of insulin receptor
2.4 Insulin synthesis and secretion
2.4.1 Structure of insulin
2.5       Synthesis of insulin
2.6       Control of insulin secretion
2.7       Complication of diabetes mellitus
2.7.1 Diabetes retinopathy
2.7.2 Diabetic nephropathy
2.7.3 Diabetic neuropathy
2.7.4 Diabetic foot
2.7.5 Stroke
2.7.6 Cardiovascular complications
2.8       Pathophysiology of diabetes mellitus
2.8.1 Diagnostic criteria for diabetes mellitus
2.9 Management/treatment of diabetes
2.9.1 Diet and exercise
2.9.2 Oral hypoglycaemic drugs
2.9.3 Recent advances in management of diabetes mellitus
2.10 Selenium yeast
2.10.1 Composition of selenium yeast
2.10.2 Function of selenium
2.10.3 Safety of selenium yeast

CHAPTER THREE
3.0 MATERIALS AND METHODS
3.1 Materials
3.1.1 Animal
3.1.2 Drug, regents and practicals
3.2 Method
3.2.1 Induction of experimental diabetes mellitus
3.2.2 Experimental design
3.2.3 Blood glucose level determination
3.2.4 Collection and preparation of serum sample for analysis
3.2.5 Estimation of serum electrolyte
3.2.6 Estimation of serum liver enzymes levels
3.2.6.1 Serum alanine aminotransferase
3.2.6.2 Serum aspartate aminotransferase
3.2.6.3 Serum alkaline phosphatase
3.2.7 Estimation of oxidative stress biomarkers
3.2.8 Measurement of superoxide dismutase (SOD) activity
3.2.9 Measurement of catalase (CAT) activity
3.2.10 Estimation of lipid peroxidation biomarker (MDA)
3.2.11 Estimation of lipid profile
3.2.12 Estimation of serum T3 and T4
3.2.13 Estimation of inflammatory markers
3.3       Statistics

CHAPTER FOUR
4.0       RESULTS
4.1       Blood Glucose Levels of Selenium Yeast Administered in Streptozotocin Induce Diabetes in Wistar Rats
4.2       Changes in Oxidative Stress and Lipid Peroxidation Biomarkers in Rats Treated with Selenium Yeast for the Period of Four Weeks in Streptozotocin        Induced Diabetes
4.3       Changes in Serum Electrolytes Levels in Rats Treated with Selenium Yeast for the Period of Four Weeks in Streptozotocin Induced Diabetes
4.4       Changes in Serum Liver Enzymes and the Inflammation Biomarker (TNF-α) in Rats Treated with Selenium Yeast for the Period of Four Weeks in Streptozotocin          Induced Diabetes
4.5       Changes in Serum Triiodothyronine, Tetraiodothyroxine and Lipid Profile of Rats Treated with Selenium Yeast in Streptozotocin Induced Diabetes

CHAPTER FIVE
5.0 Introduction
5.0.1 Induction of hyperglycaemia
5.0.2 Effects of selenium yeast on blood glucose level
5.0.3 Effects of selenium yeast on serum liver enzymes
5.0.4 Effects of selenium yeast on oxidative stress biomarkers
5.0.5 Effects of selenium yeast on the serum levels of lipid profile
5.0.6 Effects of selenium yeast on serum level of lipid peroxidation biomarkers
5.0.7 Effects of selenium yeast on the inflammation biomarkers
5.0.8 Effects of selenium yeast on serum electrolyte
5.0.9 Effects of selenium yeast on serum Triiodothyronine and Tetraiodothyronine

CHARPTER SIX
6.1       Conclusion
6.2       Recommendation
6.3       Contribution to knowledge
References
Appendices



ABSTRACT


Oxidative stress and lipid peroxidation are central factors in the metabolic dysfunctions and pathologies associated with diabetes. The results from studies on the benefits of Selenium a trace element with antioxidant, anti-lipidemic and anti-inflammatory properties, in diabetes mellitus have been controversial without prospective outcome and Se appears to be a double-edged sword in the pathologies of diabetes mellitus. It was suggested that selenium could cause glucose disturbance and increase the risk for diabetes mellitus. The present study intends to determine the ameliorative effects of selenium yeast on blood glucose level, oxidative stress and lipid peroxidation biomarkers, and abnormal lipid profile, serum levels of liver enzymes, electrolytes, triiodothyronine and tetraiodothyronine levels in streptozotocin induced diabetes in Wister rats. Thirty five (35) adult male Wistar rats weighing (180 – 200) grams randomly divided into six treatment and one control groups of five rats each (n = 5). Hyperglycemia was induced in all groups except Group IV by single intraperitoneal injection of 60mg/kg of streptozotocin dissolved in 0.1ml fresh cold citrate buffer pH 4.5 into 16 h-fasted rats. In addition, Groups I and II received 0.1 and 0.2 mg/kg/day for 4weeks of selenium yeast respectively, Group III received 1mg/kg/day for 4weeks of glibenclamide, Groups IV and V served as the normal and diabetic control groups respectively and received only 0.9% of normal saline. Groups VI and VII received 300 and 120 mg/kg/day for 4weeks of aspirin and ibuprofen respectively, all treatments were administered via oral route. Blood samples were collected from the tail vein on weekly basis for the period of 4weeks and used for determination of blood plasma glucose levels, and at the end of the fourth week rats were euthanized and blood samples were drawn from the heart by cardiac puncture and used to estimate oxidative stress biomakers (i.e. superoxide dismutase, catalase and gluthation peroxidase) and lipid peroxidation biomarkers (i.e. malondealdehyde),lipid profile, serum levels of liver enzymes, electrolytes, triiodothyronine and tetraiodothyronine levels. Analysis of variance and Turkey‟s post-hoc test were used to analyze the data obtained. The results showed that there was significant (P < 0.05) decrease in blood glucose level at week one and week three with the dose of 0.2 mg/kg of selenium yeast administered, while with the dose of 0.1mg/kg of selenium yeast, there was no significant difference in blood plasma glucose level when compared with the diabetic control group. It was also revealed that the serum liver enzymes aspertate amino transferase and alanine amino transferase were significantly higher (P < 0.05) in the groups treated with 0.1 and 0.2 mg/kg of selenium yeast. Also, of the oxidative stress biomarkers assessed, there was significant reduction (P < 0.05) in only the malondealdehyde level of the group treated with 0.2 mg/kg of selenium yeast when compared with the diabetic control group. For the lipid profile assessment, the effect of selenium yeast was only seen in the level of triglyceride in the group treated with 0.2 mg/kg of selenium yeast which was significantly lower (P < 0.05) when compared to the diabetic control. Sodium and chloride ion levels of the serum electrolytes were significantly lowered (P < 0.05) in the group treated with 0.2 mg/kg of selenium yeast when compared to diabetic control group. Serum triiodothyronine and tetraiodothyronine levels did not show any significant difference across all the treated groups when compared to the diabetic and normal control groups. Tissue necrosis factor alpha level in the serum showed a decrease in the groups treated with 0.1 and 0.2 mg/kg of selenium yeast but not statistically significant (P > 0.05) when compared with the normal and diabetic control groups. Therefore, selenium yeast possesses hypoglycaemic property that is comparable to the oral-hypoglycaemic drug glibenclamide. In addition, the effect of the 0.2 mg/kg of selenium yeast on the oxidative stress biomarkers assessed did not provide sufficient evidence to conclude that the selenium yeast used in the study elicited an antioxidant effect. The marked decline in serum triglyceride concentration in the 0.2 mg/kg of selenium yeast treated group was indicative of direct effect of the antioxidant capacity of selenium on oxidation of lipids and lipoproteins.





CHAPTER ONE

1.0 INTRODUCTION

1.1                                                                    Background of the Study

Diabetes is a common metabolic disorder characterized by hyperglycemia due to an absolute or re1lative insulin deficiency (Lawal et al., 2008; WHO, 2010). It affects essential biochemical pathways of the body including carbohydrate, protein, and lipid metabolisms. The World Health Organization (WHO), estimated that there were 171 million people in the world with diabetes in the year 2008 and this is projected to increase by over a 100% to 366 million by 2030 (WHO, 2010). Diabetes is associated with reduced life expectancy, significant high mortality and diminished quality of life. In 2005 an estimated 1.1 million people died from diabetes and diabetes complications (WHO, 2008). Its prevalence is rising globally, including the rural Nigerian populations (Ime et al., 2011).

Epidemiological reports has highlighted on the fact that low- and middle-income countries will bear the brunt of the increase and that Africa will contribute significantly to this rise. In Africa 40% of people with diabetes live in low and middle income countries causing 5% of the deaths globally each year. This is likely to increase by more than 50% in the next 10 years, if urgent action is not taken (WHO, 2007). The challenges and thus, the solutions in the provision of healthcare that would improve outcome for diabetes in low and middle income countries are many and can be found at multiple levels. Patient-related factors are of extreme importance, these ranges from low levels of self-management practices, lack of adherence to lifestyle changes and medication and lack of faith in the conventional management procedures. Many African populations still regard alternative healing systems as the primary source of healthcare or alternatively, consult both traditional or folk healers....


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