Sattarinezhad Elahe, Shafaroodi Hamed, Sheikhnouri Kiandokht, Mousavi Zahra, Moezi Leila
Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Pharmacology and Toxicology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.
Epilepsy Behav. 2014 Aug;37:36-42. doi: 10.1016/j.yebeh.2014.05.024. Epub 2014 Jun 24.
Coenzyme Q10 is a potent antioxidant in both mitochondria and lipid membranes. It has also been recognized to have an effect on gene expression. This study was designed to investigate whether acute or subchronic treatment with coenzyme Q10 altered the seizures induced by pentylenetetrazole or electroshock in mice. We also evaluated the involvement of nitric oxide in the effects of coenzyme Q10 in pentylenetetrazole-induced seizure models. Acute oral treatment with different doses of coenzyme Q10 did not affect the seizure in intraperitoneal pentylenetetrazole, intravenous pentylenetetrazole, and electroshock models in mice. Subchronic oral administration of coenzyme Q10 (100 mg/kg or more) increased time latencies to the onset of myoclonic jerks and clonic seizures induced by intraperitoneal pentylenetetrazole and at the doses of 25 mg/kg or more increased the seizure threshold induced by intravenous infusion of pentylenetetrazole. Subchronic doses of coenzyme Q10 (50 mg/kg or more) also decreased the incidence of tonic seizures in the electroshock-induced seizure model. Moreover, acute treatment with the precursor of nitric oxide synthesis, L-arginine (60 mg/kg), led to a significant potentiation of the antiseizure effects of subchronic administration of coenzyme Q10 (400 mg/kg in intraperitoneal and 6.25 mg/kg in intravenous pentylenetetrazole tests). Acute treatment with l-NAME (5 mg/kg), a nonspecific nitric oxide synthase inhibitor, significantly attenuated the antiseizure effects of subchronic doses of coenzyme Q10 in both seizure models induced by pentylenetetrazole. On the other hand, acute administration of aminoguanidine (100 mg/kg), a specific inducible nitric oxide synthase inhibitor, did not affect the seizures in mice treated with subchronic doses of coenzyme Q10 in both intraperitoneal and intravenous pentylenetetrazole tests. In conclusion, only subchronic and not acute administration of coenzyme Q10 attenuated seizures induced by pentylenetetrazole or electroshock. We also demonstrated, for the first time, the interaction between nitric oxide and coenzyme Q10 in antiseizure activity probably through the induction of constitutive nitric oxide synthase.
辅酶Q10是线粒体和脂质膜中一种有效的抗氧化剂。它也被认为对基因表达有影响。本研究旨在调查辅酶Q10急性或亚慢性治疗是否会改变小鼠戊四氮或电休克诱导的癫痫发作。我们还评估了一氧化氮在辅酶Q10对戊四氮诱导的癫痫模型作用中的参与情况。不同剂量辅酶Q10的急性口服治疗对小鼠腹腔注射戊四氮、静脉注射戊四氮和电休克模型中的癫痫发作没有影响。辅酶Q10（100mg/kg及以上）的亚慢性口服给药增加了腹腔注射戊四氮诱导的肌阵挛抽搐和阵挛性癫痫发作开始的时间延迟，并且在25mg/kg及以上的剂量增加了静脉注射戊四氮诱导的癫痫阈值。辅酶Q10的亚慢性剂量（50mg/kg及以上）也降低了电休克诱导的癫痫模型中强直性癫痫发作的发生率。此外，一氧化氮合成前体L-精氨酸（60mg/kg）的急性治疗导致辅酶Q10亚慢性给药（腹腔注射400mg/kg和静脉注射戊四氮试验中6.25mg/kg）的抗癫痫作用显著增强。非特异性一氧化氮合酶抑制剂L-NAME（5mg/kg）的急性治疗显著减弱了辅酶Q10亚慢性剂量在两种戊四氮诱导的癫痫模型中的抗癫痫作用。另一方面，特异性诱导型一氧化氮合酶抑制剂氨基胍（100mg/kg）的急性给药在腹腔注射和静脉注射戊四氮试验中对用辅酶Q10亚慢性剂量治疗的小鼠的癫痫发作没有影响。总之，只有辅酶Q10的亚慢性而非急性给药减弱了戊四氮或电休克诱导的癫痫发作。我们还首次证明了一氧化氮与辅酶Q10在抗癫痫活性中的相互作用可能是通过诱导组成型一氧化氮合酶实现的。
