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Abstract Epilepsy is one of the most common neurological disorders. It IS a life long disease which requires a life long treatment. So, it is very important to study the toxic effects of the used drugs to avoid more suffer for the patient. A major problem in the management of epileptic patients is the possibility that certain antiepileptic drugs may cause chromosomal abnormalities which may lead to birth defects and also may be involved in the development of neoplasia. On the other hand controversy still exists regarding the potential mutagenicity of these drugs. Also, there is a shortage in knowledge about the immuno toxicity of these drugs. The present work was carried out to evaluate some of the toxic effects of the most commonly used antiepileptic drugs namely Phenytoin Sodium, carbamazepine, Clonazepam, and Sodium valproate, specially their potential mutagenicity and immunotoxicity in rats. 150 adult albino rats of both sexes weighing 200 - 220 gms each were kept under the same conditions for 15 days, then they were divided into 10 groups, 15 rats ofor each group. 8 groups were used as test groups, each 2 groups of them received daily oral toxic dose of one drug from the four tested antiepileptic drugs. The toxic dose of each drug was considered as 3 folds its therapeutic dose. (119) Summary and Conclusion .... The rats of one group from each 2 groups received the same drug were sacrified after one month treatment, the rats of the other group were sacrified after 3 months. The last 2 groups of the 10 groups were used as control groups treated in the same way given daily oral dose of distilled water with no drugs. rats of one control groups were sacrified after one month and the others after 3 months. All sacrified rats either test or control rats were subjected to toxicological evaluation, by the following studies: (1) Biochemical study: (a) Liver function tests : Liver affection was evaluated by estimation of SOOT, SGPT, Alk.Ph. (b) Kidney function tests : Kidney affection was evaluated by estimation of blood urea, serum creatinine. (2) Cytogenetic study: Mutagenic effects was evaluated by studying the frequencies of structural chromosomal abnormalities (Gaps, Break, Dicentric chromosomes, Ring chromosomes, Minute fragments, and total structural) and numerical chromosomal abnormalities (Aneuploidies, polyploidies, total numerical) in rat bone marrow cells. (120) Summary and Conclusion .... (3) Immunologic study: Evaluation of the immunotoxicity was done by studying the degree of lymphocyte activation of splenic rat cells after being cultured with the mitogen phytoheamagglutinin (P.H.A.). Analysis of the results obtained revealed the following: (l) Biochemical effects : (a) Liver functions affection: Affection of the liver function indicated by increased levels of SGOT, SGPT, and Alk. Ph. to a varying degrees was observed with chronic administration of all the four drugs with the observation that sodium valproate was the most hepatotoxic drug used, clonazepam was the least hepatoloxic one, while carbamazepine and phenytoin sodium caused moderate hepatotoxicity. (b) Kidney function affection: Chronic administration of the 4 used drugs affected the renal functions indicated by increased 0 levels of blood urea and S. creatinine, to a varying degrees, with the observation that carbamazepine was the most nephrotoxic drug, phenytoin sodium was the least nephrotoxic one, while clonazepam and sodium valproate were moderately nephrotoxic. (2) Cytogenetic (Mutagenic) effects : It was observed that, in rats treated with phenytoin sodium, the frequencies of total structural and total numerical chromosomal (121) Summary and Conclusion .... aberrations were significantly increased compared to the control values after 1 and 3 months. On the other hand, the frequencies of both Structural and numerical chromosomal aberrations In rats treated with carbamazepine, clonazepam and sodium valproate were not significantly different from those in control rats. (3) Immunologic (Immunotoxic) effects: It was observed that chronic administration of phenytoin sodium caused a significant depression in the. cell mediated immune function, indicated by a significant decrease in the percentage of lymphocytes transformed into blast cells when the splenic rat cells were cultured with the mitogen phytoheamagglutinin (P.RA). On the other hand, it was observed that chronic administration of carbamazepine, clonazepam, and sodium valproate caused no significant change in the percentage of lymphocytes transformed to blast cells when the splenic rat cells were cultured with phytoheamagglutinin (P.H.A.) In conclusion : (I) The safest antiepileptic drugs, is clonazepam, which is neither mutagenic nor immunotoxic, and have a little effect on liver and moderate effect on kidney functions on chronic use. (I 22) Summary and Conclusion .... (2) The most hepatotoxic drug, is sodium valproate, while the most safe drug on the liver is clonazepam. (3) The most nephrotoxic drug, is carbamazepine, while the most safe drug on the kidney is phenytoin sodium. (4) Phenytoin sodium is potentially mutagenic on chronic use, while, clonazepam, carbamazepine and sodium valproate are not. (5) Phenytoin sodium has a potential immunotoxic effect on prolonged administration, while clonazepam, carbamazepine and sodium valproate have no effect on immune function. |