Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University, Bathinda (Punjab), India.
Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University, Bathinda (Punjab), India; Department of Pharmacology, Central University of Punjab, Bathinda (Punjab), India.
Behav Brain Res. 2022 Feb 15;419:113699. doi: 10.1016/j.bbr.2021.113699. Epub 2021 Nov 29.
Epilepsy is a neurological disease that transpires due to the unusual synchronized neuronal discharge within the central nervous system, which drives repetitious unprovoked seizures. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a complex enzyme accountable for reactive oxygen species (ROS) production, neurodegeneration, neurotoxicity, memory impairment, vitiates normal cellular processes, long term potentiation, and thus, implicated in the pathogenesis of epilepsy. Therefore, the present study was sketched to examine the neuroprotective effect of apocynin, NADPH oxidase inhibitor in pentylenetetrazole kindling epilepsy, and induced comorbidities in mice. Mice (either sex) were given pentylenetetrazole (35 mg/kg, i.p.) every other day up to 29 days, and a challenge test was executed on the 33 day. Pretreatment with apocynin (25, 50, and 100 mg/kg, i.p.) was carried out from 1 to 33 day. Rotarod and open field test were performed on the 1, 10, 20, and 30 days of the study. Animals were tutored on the morris water maze from 30 to 33 day, and the retention was registered on the 34 day. Tail suspension test and elevated plus maze were sequentially performed on the 32 and 33 day of the study. On the 34 day, animals were sacrificed, and their brains were isolated to conduct biochemical estimation. NADPH oxidase activation due to chronic pentylenetetrazole treatment resulted in generalized tonic-clonic seizures, enhanced oxidative stress, remodeled neurotransmitters' level, and resulted in comorbidities (anxiety, depression, and memory impairment). Pretreatment with apocynin significantly restricted the pentylenetetrazole induced seizure severity, ROS production, neurotransmitter alteration, and comorbid conditions by inhibiting the NADPH oxidase enzyme.
癫痫是一种神经系统疾病，由于中枢神经系统内神经元异常同步放电而发生，导致反复无诱因的发作。烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶是一种复杂的酶，负责产生活性氧（ROS）、神经退行性变、神经毒性、记忆障碍、破坏正常细胞过程、长时程增强，因此与癫痫的发病机制有关。因此，本研究旨在研究 NADPH 氧化酶抑制剂-apocynin 在戊四氮点燃癫痫和诱导小鼠共病中的神经保护作用。雄性和雌性小鼠每天腹腔注射戊四氮（35mg/kg），每隔一天一次，共 29 天，第 33 天进行挑战测试。apocynin（25、50 和 100mg/kg，腹腔注射）从第 1 天至第 33 天进行预处理。在研究的第 1、10、20 和 30 天进行转棒和旷场测试。从第 30 天到第 33 天，对动物进行 Morris 水迷宫训练，第 34 天记录保留时间。在研究的第 32 和 33 天，依次进行悬尾和高架十字迷宫测试。第 34 天，处死动物，分离大脑进行生化评估。慢性戊四氮处理导致 NADPH 氧化酶激活，引发全身性强直阵挛发作，增加氧化应激，重塑神经递质水平，并导致共病（焦虑、抑郁和记忆障碍）。apocynin 预处理通过抑制 NADPH 氧化酶显著限制戊四氮诱导的发作严重程度、ROS 产生、神经递质改变和共病情况。
