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.