Owoeye Olatunde, Adedara Isaac A, Bakare Oluwafemi S, Adeyemo Oluwatobi A, Egun Christa, Farombi Ebenezer O
Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry and.
Toxicol Mech Methods. 2014 Jun;24(5):353-61. doi: 10.3109/15376516.2014.913752. Epub 2014 May 5.
Phenytoin (PHT), an anticonvulsant agent, widely used for the treatment of epilepsy has been reported to exhibit toxic side effects. The present study investigated the protective effects of kolaviron and vitamin E on hematotoxicity and neurotoxicity induced by phenytoin, in prepubertal male rats. The animals were treated with PHT (75 mg/kg) separately or in combination with either kolaviron (200 mg/kg) or vitamin E (500 mg/kg) for 14 days. Phenytoin treatment significantly decreased the hemoglobin, white blood cells, lymphocytes and mean corpuscular volume levels without affecting red blood cell, packed cell volume, neutrophils, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration when compared with the control rats. There was a significant increase in lipid peroxidation and hydrogen peroxide levels with marked depletion in antioxidant status in brains of PHT-treated rats when compared with the control. Although PHT treatment had no effect on the granular layer, widest diameter of Purkinje cells and Purkinje layer of the cerebellum, it significantly reduced its molecular layer and the density of Purkinje cell. Administration of PHT significantly reduced the densities of the granule cells of the dentate gyrus and the pyramidal neurons of the cornu ammonis of hippocampus proper. Co-treatment with kolaviron and vitamin E effectively reversed the PHT-mediated alterations in the hematology, brain antioxidant status and histomorphometry when compared to PHT only. Taken together, the present data indicate the abilities of kolaviron and vitamin E to ameliorate phenytoin-induced hematotoxicity and oxidative stress in brains of rats.
苯妥英（PHT）是一种抗惊厥药物，广泛用于治疗癫痫，但据报道有有毒副作用。本研究调查了可乐维隆和维生素E对青春期前雄性大鼠苯妥英诱导的血液毒性和神经毒性的保护作用。动物分别用PHT（75mg/kg）单独处理或与可乐维隆（200mg/kg）或维生素E（500mg/kg）联合处理14天。与对照大鼠相比，苯妥英处理显著降低了血红蛋白、白细胞、淋巴细胞和平均红细胞体积水平，而对红细胞、红细胞压积、中性粒细胞、平均红细胞血红蛋白和平均红细胞血红蛋白浓度没有影响。与对照相比，PHT处理的大鼠大脑中脂质过氧化和过氧化氢水平显著增加，抗氧化状态明显降低。虽然PHT处理对小脑的颗粒层、浦肯野细胞的最大直径和浦肯野层没有影响，但它显著减少了其分子层和浦肯野细胞的密度。给予PHT显著降低了齿状回颗粒细胞和海马体固有角锥体神经元的密度。与仅用PHT相比，可乐维隆和维生素E联合处理有效地逆转了PHT介导的血液学、脑抗氧化状态和组织形态学变化。综上所述，目前的数据表明可乐维隆和维生素E能够改善苯妥英诱导的大鼠脑血液毒性和氧化应激。
