Institute of Medical Physiology Richard Burian, Belgrade University School of Medicine, Belgrade, Serbia.
Med Chem. 2012 Jan;8(1):59-64. doi: 10.2174/157340612799278577.
Nitric oxide (NO), one of the gaseous neurotransmitters, is produced in reaction catalyzed by family of NO synthases (NOS). The involvement of neuronal NOS (nNOS) in seizures induced by homocysteine thiolactone has not been studied. Therefore, the aim of this study was to determine the effects of 7-nitroindazole, a selective nNOS inhibitor, on behavioral manifestations of homocysteine - induced seizures in adult rats. Adult male Wistar albino rats were treated with 7-nitroindazole (25, 50 and 75 mg/kg, i.p.) 30 min before injection of subconvulsive dose of homocysteine (D,L homocysteine thiolactone 5.5 mmol/kg, i.p.). Convulsive behavior was assessed during 90 min upon homocysteine administration by the following parameters: seizure incidence, duration of latency, number of seizure episodes per rat and their severity. Severity of seizures was evaluated using a descriptive scale graded from 0 to 4. It was shown that 7-nitroindazole increased seizure incidence, shortened latency time to first seizure, increased number of seizure episodes per rat and increased severity of seizures induced by homocysteine in rats. 7- nitroindazole in dose of 25 mg/kg led to a statistically significant increase in the seizure incidence and number of seizure episodes per rat, while doses of 50 and 75 mg/kg significantly increased severity of homocysteine-induced seizures. It could be concluded that inhibition of nNOS by 7-nitroindazole potentiates seizures induced by homocysteine in rats.
一氧化氮（NO）是一种气态神经递质，由一氧化氮合酶（NOS）家族催化产生。尚未研究同型半胱氨酸硫内酯诱导的癫痫发作中神经元型一氧化氮合酶（nNOS）的参与。因此，本研究的目的是确定 7-硝基吲唑（一种选择性 nNOS 抑制剂）对成年大鼠同型半胱氨酸诱导癫痫发作的行为表现的影响。成年雄性 Wistar 白化大鼠在注射亚惊厥剂量的同型半胱氨酸（D，L 同型半胱氨酸硫内酯 5.5 mmol/kg，腹腔注射）前 30 分钟用 7-硝基吲唑（25、50 和 75 mg/kg，腹腔注射）处理。通过以下参数评估同型半胱氨酸给药后 90 分钟内的惊厥行为：癫痫发作发生率、潜伏期持续时间、每只大鼠的癫痫发作次数及其严重程度。使用从 0 到 4 分级的描述性量表评估癫痫发作的严重程度。结果表明，7-硝基吲唑增加了同型半胱氨酸诱导的大鼠癫痫发作的发生率，缩短了首次癫痫发作的潜伏期时间，增加了每只大鼠的癫痫发作次数，并增加了癫痫发作的严重程度。25mg/kg 的 7-硝基吲唑导致癫痫发作发生率和每只大鼠的癫痫发作次数呈统计学显著增加，而 50 和 75mg/kg 的剂量则显著增加了同型半胱氨酸诱导的癫痫发作的严重程度。可以得出结论，7-硝基吲唑抑制 nNOS 增强了大鼠同型半胱氨酸诱导的癫痫发作。
