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RESEARCH TOPIC – EFFECT OF AQUEOUS AND ETHANOL LEAF EXTRACTS OF ERIOSEMA PSORALEOIDES ON SOME OXIDATIVE STRESS PARAMETERS IN ALLOXAN-INDUCED DIABETIC RATS

EFFECT OF AQUEOUS AND ETHANOL LEAF EXTRACTS OF ERIOSEMA PSORALEOIDES ON SOME OXIDATIVE STRESS PARAMETERS IN ALLOXAN-INDUCED DIABETIC RATS

 

ABSTRACT

Effect of aqueous and ethanol leaf extracts of Eriosema psoraleoides on some oxidative stress parameters was investigated in normal and alloxan-induced diabetic rats. Phytochemical composition, acute toxicity screening of the two extracts was carried out. A dose of 200 mg/kg and 400 mg/kg of aqueous and ethanol extracts was given orally daily, for four days to the alloxan-induced diabetic rats. Plasma blood glucose concentrations were determined daily for one week. At the end of one week the animals were sacrificed and blood samples were taken from all the groups for the determination of some biochemical and haematological parameters. Preliminary photochemical screening of the two extracts revealed the presence of flavonoids, alkaloids, glycosides, steroids, reducing sugars, resins, tannins and saponins. Acute oxidative stress and diabetes were induced in the rats using alloxan monohydrate (130 mg/kg body weight). The acute toxicity (LD50) was 5000 mg/kg and 2900 mg/kg body weight for aqueous and ethanol extract of Eriosema psoraleoides respectively.

The data were compared statistically by using one-way analysis of variance with repeated measures and one-way analysis of variance (ANOVA). Treatment with the extracts as well as glibenclamide had no significant (P>0.05) effect on body weights of alloxan-induced diabetic rats. The extracts and glibenclamide produced significant (P<0.05) decrease in blood glucose concentrations in alloxan-induced diabetic rats. However, the extracts produced significant (P<0.05) increase in RBC, WBC, Neutrophlis, Lymphocytes and monocytes but do not have significant (P>0.05) effect on haemoglobin concentration. Administration of the extracts showed significant (P<0.05) decrease in TC, TG, HDL, LDL, MDA concentrations and SOD and CAT activities in diabetic rat when compared with diabetic untreated rats. The extracts had no significant (P>0.05) decrease on protein, GSH and Vitamin C concentrations in all the diabetic rats treated. Diabetic rats treated with glibenclamide showed significant (P<0.05) decrease in LDL, Protien, MDA concentrations and in the activity of SOD in diabetic treated rats when compared with diabetic untreated rats. The observed anti-diabetic property of the extracts suggests that Eriosema psoraleoides could be used in the management of diabetes. The active principles in the extracts might have insulin like activity, stimulating increase in peripheral glucose consumption as well as protection against oxidative damage.

 

CHAPTER ONE

INTRODUCTION

Over the years, medicinal plants are widely used in the management of diseases all over the world (Adewunmi and Ojewole 2004). Historically, the use of medicinal plants is as old as mankind and medicine. In Nigeria, several thousands of plant species have been claimed to possess medicinal properties and are employed in the treatment of many ailments (Okigbo and Mmeka, 2006). Diabetes mellitus is a disease that is associated with common metabolic disorder resulting from defects in insulin secretion, insulin action or both; it is characterized by hyperglycemia often accompanied by glycosuria, polydipsia, and polyuria (Celik et al., 2002; ADA, 2005). In diabetes, persistent hyperglycemia causes increased production of free radicals especially reactive oxygen species (ROS), for all tissues from glucose auto-oxidation and protein glycosylation (Aragno et al., 1999; Bonnefont et al., 2000).

These radicals are. However, several conditions are known to disturb the balance between ROS production and cellular defense mechanisms (Moussa, 2008). This imbalance can result in cell dysfunction and destruction resulting in tissue injury. The increase in the levels of ROS in diabetes could be due to increased production of free radicals and or decreased destruction of free radicals by nonenzymic and enzymic catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) antioxidants (Moussa, 2008). The levels of these antioxidant enzymes critically influence the susceptibility of various tissues to oxidative stress and are associated with the development of complications in diabetes (Moussa, 2008). In recent times, report from medicinal plants research indicates that extracts from plants are able to mop up ROS and reduce the effect of oxidative stress and its complications (Ceriello, 2000).

In Africa, hundreds of plants are used traditionally for the management and or control of diabetes mellitus. Unfortunately, only a few of such medicinal plants have been scientifically validated (Tanko et al., 2007). One of the plants commonly employed traditionally in the management of some disease conditions such as diabetes mellitus is Eriosema psoraleoides. This plant is widely distributed in tropical Africa and South Africa, where it is used as folklore remedies. However, there is no known scientific report of this plant hence, the thrust for its use in this present investigation. Therefore, this study is to investigate the effect of aqueous and ethanol leaf extracts of Eriosema psoraleoides on some oxidative stress parameters in alloxan-induced diabetic rats.

1.1 Diabetes mellitus

In the early years of modern medicine, diabetes was thought to be a disease of the blood, the kidney, the liver and the stomach as far as 1857, it was considered a disease that was associated with the nervous system. Although diabetes has been recognized since antiquity, and treatments of various efficacies have been known in various regions since the middle ages, and in legend for much longer, pathogenesis of diabetes has only been understood experimentally since about 1900 (Patlak, 2002). Diabetes has usually high concentration of glucose in the blood a condition known as hyperglycaemia (Nelson and Cox, 2000).

1.1.1 Types of Diabetes mellitus

There are various types of diabetes mellitus and two are based on their aetiology and clinical manifestation.

1.1.1.1 Type 1 Diabetes mellitus

Type 1 diabetes mellitus is sometimes called insulin-dependent diabetes mellitus (IDDM), immune-mediated, juvenile-onset diabetes or pancreatic endocrine insufficiency (Tuomilochto, 1992). It occurs when the body fails to produce insulin due to destruction of the insulin-producing β-cells in the pancreas. Pancreatic insufficiency starts with mass loss of insulin-producing cells leading to the drastic decrease of insulin. Type 1 diabetes mellitus is caused mostly by autoimmune attack against β-cells in the pancreas. Mass destruction of these cells can occur either without known cause or as a response to virus infections, toxins, pancreas inflammatory diseases, traumas, tumors, or stress (Wikipedia, 2011a).

(a) Aetiology of Type 1 diabetes

Aetiology of diabetes is the study of causes or causative factors in diabetes. Type 1 diabetes is a discrete disorder and its pathogenesis involves environmental toxins which triggers or may activate autoimmune responses in genetically susceptible individuals, leading to progressive loss of pancreatic islet beta cells (Harrison et al., 1999). In many aspects, attempts to explain the aetiology of Type 1 diabetes have been disappointing despite decades of research done (Harrison et al., 1999). Predisposition is mediated by a number of genes that interact in a complex manner with each other and the environment.
The fact that Finland has the world highest incidence of Type 1 diabetes, 35 cases per 100,000 women when compared with Estonica whose population is linguistically and ethnically very similar (Tuomilochto, 1992) but has only a third of the Finland incidence of Type 1 diabetes is an indication that environmental factors might have a particular powerful influence on the aetiology of Type 1 diabetes. Despite these compelling epidemiological findings, the environmental factor(s) that precipitated Type 1 diabetes in genetically susceptible individuals have remained speculative, although dairy products and early weaning onto cow’s milk, and increased dietary nitrate and nitrite have been suggested to be associated factors (Tuomilochto et al., 1997).

The environmental agents that cause this injury are difficult to identify owing to the long period between exposure and the onset of hyperglycaemia. Iron could be toxic to insulin-producing cells by promoting free radical mediated stress; up to 80% of people with haemochromatosis develop diabetes. Men with high iron store (low transferring receptor, ferritin ratio) have 25-fold increase in the risk of developing diabetes (Tuomilochto et al., 1997).

(b) Common symptoms of Type 1 diabetes
Subjects with Type 1 diabetes may develop symptoms such as;
i. Blurred Vision: When there is an increase in blood sugar level, fluid may be pulled from tissue including those from the lenses of the eyes. This could affect the ability to focus.
ii. Fatigue: If the body cells are deprived of sugar, it could lead to tiredness and irritation could occur.
iii. Polydipsia and polyuria: When excessive sugar builds up in the blood stream, fluids are pulled from tissues and may result in thirst. As a result, more fluid (water) would be taken which could lead to frequent urination.
iv. Polyphagia: When there is insufficient insulin in the body to move sugar into the body cells, muscles and organs become depleted of energy. This triggers intense hunger that may persist even after a meal.
v. Weight loss: Despite eating more than usual to relieve constant hunger, weight loss is experienced.

(c) Risk factors for Type 1 diabetes
i. Age: Approximately half of the people diagnosed with Type 1 diabetes are under 20. The peak incidence is about 11 years of age.
ii. Genetic predisposition: Due to the defects of some genes the body may start autoimmune aggression towards the cells of the pancreas moreover, regenerative ability of β-cells decreases.
iii. Hereditary: One with one first-degree or two first-degree relatives has a greater risk of developing this condition.
iv. Race: All the races are affected by Type 1 diabetes, but more common with the white population especially the Northern European and less common in Asian origin (Harrison et al., 1999).

(d) Management of Type 1 diabetes
The immediate goal is to treat diabetic ketoacidosis and high blood glucose levels. Because Type 1 diabetes can start suddenly and have severe symptoms, people who are newly diagnosed are given long-term goals of treatment to: Prolong life, reduce symptoms and prevent diabetes-related complications such as blindness, heart disease, kidney failure and amputation of limbs. These goals in managing Type 1 diabetes are accomplished through: Blood pressure and cholesterol control, careful self testing of blood glucose levels, education, exercise, foot care, meal planning and weight control, medication or insulin use.

 

EFFECT OF AQUEOUS AND ETHANOL LEAF EXTRACTS OF ERIOSEMA PSORALEOIDES ON SOME OXIDATIVE STRESS PARAMETERS IN ALLOXAN-INDUCED DIABETIC RATS

 

1.1.1.2 Type 2 Diabetes mellitus

Type 2 diabetes mellitus is also known as insulin resistance, abnormal insulin secretion or non-pancreatic insufficiency. In Type 2 diabetes insulin is produced in normal or even high amounts but response of the body cells to insulin is defective, which leads to insulin resistance. Sometimes, insulin resistance is accompanied by an insulin deficiency. Type 2 diabetes has an adult onset. People with Type 2 diabetes are not dependent on exogenous insulin, but may require it for control of blood glucose concentration if this is not achieved with diet or with oral hypoglycaemic agents (Zimmet, 1992).
(a) Aetiology of Type 2 diabetes The term Type 2 diabetes has replaced several former terms, including adult-onset diabetes, obesity-related diabetes, and non-insulin-dependent diabetes mellitus (NIDDM). The epidemic of diabetes is related to Type 2 diabetes, it occurs in both developed and developing nations (Zimmet, 1992).

Type 2 diabetes is most commonly associated with a sedentary life style, bad habits and obesity. It is also common in people older than 45 years of age who are overweight. However, as a consequence of increased obesity among the young is becoming more common in children and young adults. Type 2 diabetes is the most common type of diabetes and accounts for 90-95% of all diabetes. (b) Common symptoms of Type 2 diabetes
Blurred vision, decreased libido, foul smell when urinating, fruity or sweet smell breath, numbness or tingling in the feet or hands, polydipsia, polyuria, significant water loss due to urination, stomach cramps, weight gain and wounds may not heal fast. (c) Risk factor for Type 2 diabetes i. Age: Nearly all people diagnosed with Type 2 diabetes are over 45 years. ii. Genetic predisposition increases the risk of developing type 2 diabetes to six times. iii. Hereditary: Type 2 diabetes is often genetic. iv. Obesity: Excessive weight is one of the key factors of type 2 diabetes development. Type 2 diabetes onset is two-fold higher in grade I obesity, five-fold higher in grade II obesity, and more than ten-fold higher in grade III obesity. v. Race: The Native Americans, Asians, African Caribbean descent and specific Islander groups are amongst the populations who are at increase risk of Type 2 Diabetes. vi. Women with gestational diabetic: Have increase risk of Type 2 diabetes

EFFECT OF AQUEOUS AND ETHANOL LEAF EXTRACTS OF ERIOSEMA PSORALEOIDES ON SOME OXIDATIVE STRESS PARAMETERS IN ALLOXAN-INDUCED DIABETIC RATS

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