Department of Pharmacology, All India Institute of Medical Sciences, New Delhi 110029, India.
Eur J Pharmacol. 2010 Oct 10;644(1-3):106-12. doi: 10.1016/j.ejphar.2010.07.022. Epub 2010 Jul 24.
The antiepileptic drugs, phenobarbitone and carbamazepine are well known to cause cognitive impairment on chronic use. The increase in free radical generation has been implicated as one of the important mechanisms of cognitive impairment by antiepileptic drugs. Curcumin has shown antioxidant, anti-inflammatory and neuro-protective properties. Therefore, the present study was carried out to investigate the effect of chronic curcumin administration on phenobarbitone- and carbamazepine-induced cognitive impairment and oxidative stress in rats. Pharmacokinetic interactions of curcumin with phenobarbitone and carbamazepine were also studied. Vehicle/drugs were administered daily for 21days to male Wistar rats. Passive avoidance paradigm and elevated plus maze test were used to assess cognitive function. At the end of study period, serum phenobarbitone and carbamazepine, whole brain malondialdehyde and reduced glutathione levels were estimated. The administration of phenobarbitone and carbamazepine for 21days caused a significant impairment of learning and memory as well as an increased oxidative stress. Concomitant curcumin administration prevented the cognitive impairment and decreased the increased oxidative stress induced by these antiepileptic drugs. Curcumin co-administration did not cause any significant alteration in the serum concentrations of both phenobarbitone as well as carbamazepine. These results show that curcumin has beneficial effect in mitigating the deterioration of cognitive functions and oxidative damage in rats treated with phenobarbitone and carbamazepine without significantly altering their serum concentrations. The findings suggest that curcumin can be considered as a potential safe and effective adjuvant to phenobarbitone and carbamazepine therapy in preventing cognitive impairment associated with these drugs.
抗癫痫药物苯巴比妥和卡马西平在慢性使用时已知会引起认知障碍。自由基生成的增加被认为是抗癫痫药物引起认知障碍的重要机制之一。姜黄素具有抗氧化、抗炎和神经保护作用。因此，本研究旨在探讨慢性姜黄素给药对苯巴比妥和卡马西平诱导的大鼠认知障碍和氧化应激的影响。还研究了姜黄素与苯巴比妥和卡马西平的药代动力学相互作用。雄性 Wistar 大鼠每天给予载体/药物 21 天。使用被动回避范式和高架十字迷宫测试来评估认知功能。研究期末，测定血清苯巴比妥和卡马西平、全脑丙二醛和还原型谷胱甘肽水平。苯巴比妥和卡马西平连续给药 21 天导致学习和记忆功能显著受损，并增加氧化应激。同时给予姜黄素可预防这些抗癫痫药物引起的认知障碍和增加的氧化应激。姜黄素的共同给药未导致血清中苯巴比妥和卡马西平浓度发生任何显著变化。这些结果表明，姜黄素在减轻苯巴比妥和卡马西平治疗大鼠的认知功能恶化和氧化损伤方面具有有益作用，而不会显著改变其血清浓度。这些发现表明，姜黄素可被视为预防这些药物相关认知障碍的苯巴比妥和卡马西平治疗的潜在安全有效辅助药物。
