ABSTRACT

Cognitive deficit is an emerging health concern in diabetic patients. Hyperglycemia and reactive

oxygen species are believed to be among the prime candidates mediating the behavioral

impairments and memory deficits. The aim of this study was to evaluate the effect of curcumin on

blood glucose level, neurobehavioral responses and some oxidative stress biomarkers in Alloxan-

induced diabetic Swiss Albino mice. The animals were divided into five (5) groups of four mice

each (n=4). Diabetes was induced using a single dose of Alloxan (150 mg/kg) intra peritoneally.

Group Iserved as normoglycemic control and received distilled water, group II, III, IV and V were

diabetic and received olive oil 1 ml/kg, glibenclamide 1 mg/kg, curcumin 50 mg/kg and curcumin

100mg/kg respectively. All administrations were done for a duration of 21 days. Blood glucose

level was determined using glucose oxidase method and cognitive impairment was determined

using spontaneous alternation in the Y-maze and novel object recognition task (NORT). The result

obtained from this study showed that curcumin at both doses (50 mg/kg and 100 mg/kg) decrease

significantly (p < 0.05) the fasting blood glucose level (108.25 ± 16.01 mg/dl and 114.75 ± 5.56

mg/dl respectively) when compared with the diabetic control group (221.50 ± 14.03 mg/dl). Also

the result demonstrated that curcumin at 100 mg/kg significantly(p <0.05)increasethe percentage

alternation (74.39 ± 8.06%) when compared with the diabetic control group (47.50 ± 13.65%) in

the Y- maze test and significantly (p < 0.05) improve the memory, recognition and discrimination

indices (14.85 ± 6.46s, 0.39 ± 0.04s and 63.71 ± 2.95s) compared to the pretreatment (-10.90 ±

6.40s, -0.27 ± 0.11s and 36.04 ± 8.19s respectively) using NORT. Also, both doses of curcumin

recorded increase in SOD (12.84 ± 0.84) and catalase (85.05 ± 3.23) compared to the diabetic

control group (5.75 ± 0.96 and 62.27 ± 7.07) respectively. The findings of this study suggest that

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CHAPTER ONE

1.0       INTRODUCTION

Diabetes mellitus has been considered as one of the major health concerns all around the world

today (Stoler et al., 2008). Experimental animal models are one of the best strategies for the

understanding of pathophysiology of any disease in order to design and develop the drugs for its

treatment (Chatzigeorgiou et al., 2009). Numerous animal models have been developed for the

past few decades for studying diabetes mellitus and testing anti-diabetic agents that include

chemical, surgical and genetic manipulations (Etuk, 2012). One of the most potent methods to

induce experimental diabetes mellitus is chemical induction by Alloxan (Tyberg et al., 2001). It is

a well- known diabetogenic agent that is used to induce Type I diabetes in experimental animals

(Viana et al., 2004).

Diabetes mellitus is recognized by chronic hyperglycaemia and is associated with long term

damage, dysfunction and failure of various body organs by involvement of micro and macro-

vasculature (Hink et al., 2005). The micro-vascular involvement mostly effects retina, renal

glomeruli and peripheral nerves, while macro-vascular involvement results in dyslipidemia,

formation of reactive oxygen species (ROS), advance glycation end product (AGEs), platelet

hyper-reactivity and endothelial dysfunction (Cosentino et al., 2003). Disturbance in endothelial

function and coagulation pathway may lead to platelet activation, adhesion and aggregation

(Ronald and Goldberg, 2012).

A large number of anti-diabetic medicines are available in the pharmaceutical market for diabetes

and its related complications; however, currently no effective therapy is available to cure the

disease (Sundaram and Mitra, 2007). WHO Expert Committee on Diabetes has recommended

investigatingtraditional herbal medicines, and in this regard morethan 400 medicinal plant species

1

have been compiled (WHO, 2010). These herbal products are gaining popularity in developing

and developed countries due to their lesser side effects and low cost (Sundaram and Mitra, 2007).

Cognitive function is defined as cerebral activities that lead to knowledge, including all means and

mechanisms of acquiring information. It encompass reasoning, memory, attention, and language

and lead directly to the attainment of information and thus, knowledge. Cognitive impairments in

the diabetic population are emerging problems that warrant immediate research attention.

Evidences from neurocognitive tests suggest that cognitive dysfunction should belisted along with

retinopathy, neuropathy, nephropathy and cardiovascular complications as one of the

complications of diabetes (Sima, 2010).

The major concerns regarding cognitive impairments in the diabetic population are the associated

dramatic rise in morbidi