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

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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.
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