Abdel-Salam Omar M E, Sleem Amany A, Sayed Marawan Abd El Baset Mohamed, Youness Eman R, Shaffie Nermeen
Department of Toxicology and Narcotics, National Research Centre, Tahrir Street, Dokki, Cairo, Egypt.
Department of Pharmacology, Tahrir Street, Dokki, Cairo, Egypt.
Neurochem Res. 2020 May;45(5):1045-1061. doi: 10.1007/s11064-020-02979-3. Epub 2020 Feb 8.
The transient receptor potential vanilloid-1 (TRPV1) receptor has been implicated in the development of epileptic seizures. We examined the effect of the TRPV1 agonist capsaicin on epileptic seizures, neuronal injury and oxidative stress in a model of status epilepticus induced in the rat by intraperitoneal (i.p.) injections of pentylenetetrazole (PTZ). Capsaicin was i.p. given at 1 or 2 mg/kg, 30 min before the first PTZ injection. Other groups were i.p. treated with the vehicle or the anti-epileptic drug phenytoin (30 mg/kg) alone or co-administered with capsaicin at 2 mg/kg. Brain levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, and paraoxonase-1 (PON-1) activity, seizure scores, latency time and PTZ dose required to reach status epilepticus were determined. Histopathological assessment of neuronal damage was done. Results showed that brain MDA decreased by treatment with capsaicin, phenytoin or capsaicin/phenytoin. Nitric oxide decreased by capsaicin or capsaicin/phenytoin. GSH and PON-1 activity increased after capsaicin, phenytoin or capsaicin/phenytoin. Mean total seizure score decreased by 48.8% and 66.3% by capsaicin compared with 78.7% for phenytoin and 69.8% for capsaicin/phenytoin treatment. Only phenytoin increased the latency (115.7%) and threshold dose of PTZ (78.3%). Capsaicin did not decrease the anti-convulsive effect of phenytoin but prevented the phenytoin-induced increase in latency time and threshold dose. Neuronal damage decreased by phenytoin or capsaicin at 2 mg/kg but almost completely prevented by capsaicin/phenytoin. Thus in this model of status epilepticus, capsaicin decreased brain oxidative stress, the severity of seizures and neuronal injury and its co-administration with phenytoin afforded neuronal protection.
瞬时受体电位香草酸亚型1（TRPV1）受体与癫痫发作的发生有关。我们在通过腹腔注射戊四氮（PTZ）诱导的大鼠癫痫持续状态模型中，研究了TRPV1激动剂辣椒素对癫痫发作、神经元损伤和氧化应激的影响。在首次注射PTZ前30分钟，腹腔注射1或2 mg/kg的辣椒素。其他组分别腹腔注射溶剂、抗癫痫药物苯妥英（30 mg/kg），或与2 mg/kg辣椒素联合给药。测定脑内丙二醛（MDA）、还原型谷胱甘肽（GSH）、一氧化氮水平以及对氧磷酶-1（PON-1）活性、癫痫发作评分、潜伏期和达到癫痫持续状态所需的PTZ剂量。进行神经元损伤的组织病理学评估。结果显示，辣椒素、苯妥英或辣椒素/苯妥英联合治疗可降低脑内MDA水平。辣椒素或辣椒素/苯妥英联合治疗可降低一氧化氮水平。辣椒素、苯妥英或辣椒素/苯妥英联合治疗后，GSH水平和PON-1活性升高。与苯妥英治疗组降低78.7%和辣椒素/苯妥英联合治疗组降低69.8%相比，辣椒素治疗组平均总癫痫发作评分分别降低48.8%和66.3%。只有苯妥英可增加潜伏期（115.7%）和PTZ阈值剂量（78.3%）。辣椒素不会降低苯妥英的抗惊厥作用，但可防止苯妥英引起的潜伏期和阈值剂量增加。2 mg/kg的苯妥英或辣椒素可减轻神经元损伤，但辣椒素/苯妥英联合治疗几乎可完全预防神经元损伤。因此，在该癫痫持续状态模型中，辣椒素可降低脑氧化应激、癫痫发作严重程度和神经元损伤，且与苯妥英联合给药可提供神经元保护作用。
