EFFECT OF VITAMIN E AND RESVERATROL ON OXIDATIVE STRESS AND HAEMATOLOGICAL PARAMETERS OF CARBAMAZEPINE-INDUCED OXIDATIVE STRESS IN MALE WISTAR RATS

EFFECT OF VITAMIN E AND RESVERATROL ON OXIDATIVE STRESS AND HAEMATOLOGICAL PARAMETERS OF CARBAMAZEPINE-INDUCED OXIDATIVE STRESS IN MALE WISTAR RATS

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ABSTRACT

Carbamazepine (CBZ) is a drug used in the treatment of epilepsy and neuropathic pain. Carbamazepine induces oxidative stress and haematological toxicity. Resveratrol, known as 3,5,4′-trihydroxystilbene, is found in grapes and other plant products. Resveratrol effectively scavenges free radicals and other oxidants. Vitamin E a lipid soluble antioxidant present in all cellular membranes. The present study was designed to assess the effect of vitamin E and resveratrol on oxidative stress biomarkers and hematological parameters of carbamazepine-induced oxidative stress in male Wistar rats. Adult male Wistar rats (n = 35) were grouped into seven (7) of five (5) rats each: Group I (control) received distilled water; Group II received 2 ml/kg of corn oil; Group III received 10g/L of carboxymethylcellulose; Group IV received 50 mg/kg of carbamazepine; Group V received 50 mg/kg of carbamazepine and 200 mg/kg of Vitamin E; Group VI received 50 mg/kg of carbamazepine and 20 mg/kg of Resveratrol; Group VII received 50 mg/kg of carbamazepine and the co-administration of vitamin E at 200 mg/kg and Resveratrol at 20 mg/kg. Administration was done orally for forty five (45) days. At the end of the experiment, the animals were sacrificed and the blood samples and its serum were used for haematological and biochemical analyses, respectively. The result of the present study revealed that carbamazepine significantly (p<0.01) decreased the levels SOD, CAT and GPx to 2.04+0.02, 46.60+0.40, 42.20+0.49 respectively in comparison to control group. Treatment with carbamazepine also significantly (p<0.01) decreased RBCs, PCV, PLT, and WBCs to 6.85+0.28, 39.08+1.66, 256.00+12.20, 4.20+0.21 respectively when compared to the control group. Whereas carbamazepine significantly (p<0.01) increased MDA levels to 1.42+0.04 when compared to control group. Administration of vitamin E significantly (p<0.01) increased SOD, CAT and GPx, to 2.42±0.05, 51.80±0.49, 47.60±0.40 respectively and there was reduction in MDA (1.02±0.05) when compared to CBZ treated group. Administration of vitamin E significantly (p<0.05) increased PLT (323.20±23.83), non-significant increase in PCV (42.40±0.76) and WBCs (4.80±0.41) in comparison to CBZ treated group. Administration of resveratrol significantly (p<0.01) increased SOD, CAT and GPx, to 2.48±0.05, 53.20±0.37, 48.80±0.37, respectively and reduced MDA level to 0.98±0.05 when compared to CBZ treated group. Administration of resveratrol significantly (p<0.01) increased RBC(8.14±0.21), PCV(48.88±1.43), PLT(338.20±3.98) and WBC(5.32±0.20) in comparison to CBZ-treated group. The co-administration of vitamin E (200mg/kg) and resveratrol (20mg/kg) revealed a significant (p<0.01) increase in SOD (2.52±0.04), CAT (54.00±0.31and GPx (49.20±0.66) and significant (p<0.01) reduction in MDA (0.98±0.05) in comparison to CBZ-treated group. Co-administration of vitamin E and resveratrol significantly (p<0.01) increased RBC (8.53±0.15), PCV (50.70±0.86), PLT (361.80±8.46) and WBC (5.90±0.18) when compared to CBZ-treated group. The present results support that vitamin E and resveratrol or their combination ameliorated carbamazepine induced oxidative stress in male Wistar rats.

CHAPTER ONE

1.0       Introduction

1.1       Background of the study

Whenever a cell’s internal environment is perturbed by diseases, toxins or nutritional imbalance,

mitochondria diverts electron flow away from itself, forming reactive oxygen species (ROS) and

reactive nitrogen species (RNS), thus lowering oxygen consumption. This “oxidative shielding”

acts as a defence mechanism for either decreasing cellular uptake of toxic pathogens or

chemicals from the environment, or to kill the cell by apoptosis and thus avoid the spreading to

neighbouring cells. Therefore, ROS formation is a physiological response to stress (Basir et al.,

2005). The term “oxidative stress” has been used to define a state in which ROS and RNS reach

excessive levels, either by excess production or insufficient removal.

Epilepsy is a chronic neurological disorder characterized by seizures (Chang and Lowenstein,

2003). Many people with epilepsy have more than one type of seizures and may have other

symptoms of neurological problems as well. Several antiepileptic drugs (AEDs) have been

developed, but only a few of them have become established. It has been estimated that the

majority of epileptic patients are treated with only four drugs viz.: phenobarbital, phenytoin,

carbamazepine (CBZ) and valproic acid (BIaler and White, 2010).


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