Department of drug radiation research, National Centre for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt.
Department of pharmacology and toxicology, faculty of pharmacy, Cairo University, Kasr El-Aini St., Cairo 11562, Egypt; Department of Pharmacology and Biochemistry, The British University in Egypt, Suez Desert Road, P.O. Box 43, El Sherouk City, Cairo 11837, Egypt.
Life Sci. 2018 Nov 1;212:261-266. doi: 10.1016/j.lfs.2018.10.007. Epub 2018 Oct 6.
The current study evaluates the anticonvulsant effect of valproic acid (VPA) alone or combined with low dose γ-irradiation (LDR) against pentylenetetrazol-induced convulsions in rats.
Five groups of rats were used, group I served as normal control, group II served as PTZ- control and the other three groups were pretreated with single LDR(o.5 Gy), VPA(150 mg/kg i.p.5 days) and VPA with LDR respectively before PTZ injection. Racine score, latency and duration of convulsions were assessed. Evaluation of brain neurotransmitters (glutamate and GABA) as well as AKT/m-TOR pathway (protein kinase B [AKT], mammalian target of rapamycin [m-TOR], protein S6 and caspase 3). Measurement of oxidative stress (Malondialdehyde, glutathione and nitric oxide) was carried out. Histopathological examinations of hippocampi were done.
PTZ resulted in behavioural changes (high Racine score, long seizure duration and short latency).PTZ enhanced oxidative stress state (high MDA and NO, as well as low GSH) compared to normal control. VPA alone or combined with LDR ameliorated, the convulsions and caused significant improvement in behavioural changes and other tested parameters compared to normal control. Histopathological examination of hippocampi was carried out to adjoin the biochemical changes. Certain changes were observed after PTZ injection. However, normal pictures of the other tested groups.
The previously mentioned findings support that LDR purveyed novel anticonvulsant activity which could offer a possible contributor in the basic treatment of convulsions. This effect might be due to modulation of AkT/m-TOR pathway, reduction of oxidative stress and modulation of neurotransmitters.
本研究评估丙戊酸（VPA）单独或与低剂量γ辐射（LDR）联合治疗戊四氮（PTZ）诱导的大鼠惊厥的抗惊厥作用。
使用五组大鼠，第 I 组作为正常对照组，第 II 组作为 PTZ 对照组，另外三组分别在 PTZ 注射前用单次 LDR（0.5Gy）、VPA（150mg/kg ip 5 天）和 VPA 加 LDR 预处理。评估惊厥评分、潜伏期和持续时间。评估脑神经递质（谷氨酸和 GABA）以及 AKT/m-TOR 通路（蛋白激酶 B [AKT]、雷帕霉素靶蛋白 [m-TOR]、蛋白 S6 和半胱天冬酶 3）。测定氧化应激（丙二醛、谷胱甘肽和一氧化氮）。对海马进行组织病理学检查。
PTZ 导致行为改变（高 Racine 评分、长癫痫持续时间和短潜伏期）。与正常对照组相比，PTZ 增强了氧化应激状态（高 MDA 和 NO，以及低 GSH）。VPA 单独或与 LDR 联合治疗可改善惊厥，并显著改善行为变化和其他测试参数与正常对照组相比。对海马进行组织病理学检查以附加生化变化。PTZ 注射后观察到某些变化，但其他测试组的正常图片。
上述发现支持 LDR 提供了新的抗惊厥活性，这可能为惊厥的基本治疗提供一种可能的贡献。这种作用可能是由于 AKT/m-TOR 通路的调节、氧化应激的减少和神经递质的调节。
