Department of Drug Radiation Research, National Centre for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Toxicol Mech Methods. 2022 Jan;32(1):18-26. doi: 10.1080/15376516.2021.1956032. Epub 2021 Jul 26.
The current study evaluates the anticonvulsant effect low dose whole body gamma irradiation (LDR) alone or combined with topiramate against pentylenetetrazole (PTZ)-induced convulsions. Male Wister rats received either saline or PTZ (75 mg/kg i.p.). The other three groups were pretreated with single low dose radiation (0.5 Gy), topiramate (50 mg/kg, p.o., seven days) and TPM with LDR respectively before PTZ injection. Racine' score, latency, and duration of the convulsions were assessed. Glutamate and GABA were measured. AKT/m-TOR signaling pathway including AKT (protein kinase B), mammalian target of rapamycin (m-TOR), protein S6, and caspase 3 were also assessed. Measurements of markers of oxidative stress including malondialdehyde (MDA), glutathione (GSH), and nitric oxide (NO) were carried out. Histological examinations of hippocampi were done. PTZ produced behavioral changes (high Racine score, short latency, and long duration). It elevated MDA and NO contents, while reduced GSH content. TPM treatment alone or combined with LDR ameliorated the PTZ-induced convulsions and caused significant improvement in behavioral changes, brain mediators, m-TOR pathway, oxidative stress, and histological pictures in hippocampal regions. Histopathological examinations of the normal group showed normal structure with intact cells, while PTZ-treated rats exhibited necrosis, pyknosis, and atrophy of pyramidal cells. The histological findings corroborated with the amendment of biochemical parameters. The positive effects of LDR could offer a possible contributor in management of convulsions due to modulation of AkT/m-TOR signaling pathway, reduction of oxidative stress and modulation of brain amino acids. LDR improved the oxidative stress side effects of topiramate.
本研究评估了低剂量全身伽马照射（LDR）单独或联合托吡酯（TPM）对戊四氮（PTZ）诱导的惊厥的抗惊厥作用。雄性 Wistar 大鼠接受生理盐水或 PTZ（75mg/kg，ip）。另外三组大鼠分别在 PTZ 注射前用单次低剂量辐射（0.5Gy）、托吡酯（50mg/kg，po，七天）和 TPM+LDR 预处理。评估了 Racine 评分、潜伏期和惊厥持续时间。测量了谷氨酸和 GABA。还评估了 AKT/m-TOR 信号通路，包括 AKT（蛋白激酶 B）、雷帕霉素的哺乳动物靶标（m-TOR）、蛋白 S6 和半胱天冬酶 3。进行了包括丙二醛（MDA）、谷胱甘肽（GSH）和一氧化氮（NO）在内的氧化应激标志物的测量。对海马进行了组织学检查。PTZ 引起行为改变（高 Racine 评分、潜伏期短和持续时间长）。它增加 MDA 和 NO 含量，同时降低 GSH 含量。TPM 单独或与 LDR 联合治疗可改善 PTZ 诱导的惊厥，并显著改善行为变化、脑介质、m-TOR 通路、氧化应激和海马区的组织学图片。正常组的组织病理学检查显示细胞完整的正常结构，而 PTZ 处理的大鼠表现出坏死、固缩和锥体细胞萎缩。组织学发现与生化参数的修正相符。LDR 通过调节 AKT/m-TOR 信号通路、减少氧化应激和调节脑氨基酸，可以为治疗惊厥提供一种可能的方法。LDR 改善了托吡酯的氧化应激副作用。
