Asehinde Stephen, Ajayi Abayomi, Bakre Adewale, Omorogbe Osarume, Adebesin Adaeze, Umukoro Solomon
Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Basic Clin Neurosci. 2018 Nov-Dec;9(6):389-396. doi: 10.32598/bcn.9.6.389. Epub 2018 Nov 3.
Isoniazid-induced seizure, often described as Status Epilepticus (SE), is an emergency condition characterized by repeated convulsive episodes that responds poorly to the currently available anticonvulsant drugs. The current study aimed at ascertaining the effect of Jobelyn (JB), an African dietary supplement, on seizures, altered oxidative stress, and glutamate decarboxylase activity induced by isoniazid in mice.
A total of 6 mice received JB (10-50 mg/kg, PO), pyridoxine (300 mg/kg), diazepam (5 mg/kg), or distilled water (10 mL/kg) 30 minutes prior to the induction of SE with injection of isoniazid (300 mg/kg, IP). Thereafter, the mice were observed for the onset of convulsions for a period of two hours. Moreover, the effect of JB on Glutamate Decarboxylase (GAD) activity and biomarkers of oxidative stress (glutathione and malondialdehyde) was also evaluated in the brain homogenates of another set of isoniazid-treated mice.
JB (50 mg/kg, PO) prolonged the latency to convulsions, but could not prevent the occurrence of seizure episodes caused by isoniazid. Moreover, JB neither showed any protection against death nor delayed the latency to death caused by isoniazid. However, this dose of JB positively modulated the concentrations of malondialdehyde and glutathione in the brains of mice treated with isoniazid. The activity of GAD, the enzyme responsible for GABA synthesis, increased by JB, which suggested enhanced GABAergic neurotransmission.
The current study findings suggest that JB prolongs the latency to convulsions, enhances GABAergic neurotransmission, and demonstrates anti-oxidative effect in isoniazid-treated mice.
异烟肼诱发的癫痫发作，常被描述为癫痫持续状态（SE），是一种紧急情况，其特征为反复惊厥发作，对目前可用的抗惊厥药物反应不佳。本研究旨在确定一种非洲膳食补充剂乔贝林（JB）对异烟肼诱导的小鼠癫痫发作、氧化应激改变及谷氨酸脱羧酶活性的影响。
总共6只小鼠在腹腔注射异烟肼（300mg/kg）诱导SE前30分钟，分别接受JB（10 - 50mg/kg，口服）、吡哆醇（300mg/kg）、地西泮（5mg/kg）或蒸馏水（10mL/kg）。此后，观察小鼠抽搐发作情况两小时。此外，还在另一组接受异烟肼治疗的小鼠脑匀浆中评估了JB对谷氨酸脱羧酶（GAD）活性及氧化应激生物标志物（谷胱甘肽和丙二醛）的影响。
JB（50mg/kg，口服）延长了惊厥潜伏期，但未能预防异烟肼引起的癫痫发作。此外，JB既未显示出对死亡的任何保护作用，也未延迟异烟肼导致的死亡潜伏期。然而，该剂量的JB可正向调节异烟肼处理小鼠脑中丙二醛和谷胱甘肽的浓度。负责γ-氨基丁酸（GABA）合成的GAD活性因JB而增加，这表明GABA能神经传递增强。
本研究结果表明，JB可延长惊厥潜伏期，增强GABA能神经传递，并在异烟肼处理的小鼠中表现出抗氧化作用。
