EFFECTS OF ADMINISTRATION OF CARBAMAZEPINE, PHENYTOIN AND THEIR COMBINATION ON NEUROBEHAVIOURAL, COGNITIVE HAEMATOLOGICAL AND SERUM BIOCHEMICAL CHANGES IN ALBINO RATS
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ABSTRACT
The aim of the study was to evaluate the neurobehavioural patterns, cognitive functions and haemato-biochemical changes following the administration of carbamazepine (CBZ), phenytoin (PHE) and their combination. Forty, apparently healthy adult male Albino rats weighing between 144 and 300 g were divided into four groups of 10 animals each and used for the experiment. Group I (control) were administered distilled water per os at the dose rate of 10 mls/kg and they served as untreated control. CBZ at 20 mg/kg, PHE at 100 mg/kg and a combination of CBZ and PHE at 20 mg/kg and 100 mg/kg were administered per os to groups II, III and IV respectively. The regimens were given once daily for a period of eight weeks and the rats were monitored for neurobehavioural changes and cognitive functions using the method as described by Zhu et al., 2001. Blood and serum samples were collected for evaluation of full blood count, total protein, albumin, globulin, urea and some electrolytes. Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase activities were also determined. Results show that the administration of CBZ, PHE and their combination induced cognitive impairments. Combination of the drugs caused significant (P < 0.05) memory impairment. Locomotion of the rats administered CBZ decreased significantly at weeks 5, 7 (P < 0.01) and 2 (P < 0.05) when compared to week 1 of therapy, but increased at weeks 6 and 8 compared with week 1. The group administered CBZ+PHE had decreased locomotion at weeks 2, 5 (P < 0.05) and 8 (P < 0.01) when compared with week 1 and increased at weeks 4, 7 (P < 0.05) compared with week 1 also, at week 4 (P < 0.01) compared with week 3. Rearing activity reduced in the CBZ-treated group at weeks 4, 7 (P < 0.05) and week 5 (P < 0.01) compared to week 1. A significant (P < 0.05) 8 increase was observed at week 5 and a decrease (P < 0.05) at week 7 when the two weeks were compared to week 1 with the administration of the drug combination. There was no significant (P < 0.05) change in the value of the PCV and Hb but the RBC and platelets decreased in all the drug-treated groups. Leucocytosis, lymhpocytosis and neutrophilia were recorded in all the rats treated with either or combination of CBZ and PHE. Increased Na+ and decreased K+ were observed in the drug-treated groups, whereas Clremained unaltered. Generally, there were increases in serum proteins, albumin and urea as globulin decreased. There was a significant increase in ALT activities in the CBZ and CBZ+PHE groups and an increase in AST activity in the PHE group. In conclusion, the administration of CBZ, PHE and their combination affect cognitive, neurobehaviour, serum biochemical and haematologic parameters. It is recommended that serum biochemical and haematological parameters must be observed and evaluated for all individuals undergoing therapy with CBZ, PHE or their combination as their effects are deleterious with use of over 8 weeks.
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