Endothelial nitric oxide synthase activity involves in the protective effect of ascorbic acid against penicillin-induced epileptiform activity

Abstract

Ascorbic acid and nitric oxide are known to play important roles in epilepsy. The aim of present study was to identify the involvement of nitric oxide (NO) in the anticonvulsant effects of ascorbic acid on penicillin-induced epileptiform activity in rats. Intracortical injection of penicillin (500, International Units (IU)) into the left sensorimotor cortex induced epileptiform activity within 2-5 min. Thirty minutes after penicillin injection, nitric oxide synthase (NOS) inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME, 100mg/kg), neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (7-NI, 40 mg/kg), NO substrate, l-arginine (500 mg/kg) were administered with the most effective dose of ascorbic acid (100 mg/kg) intraperitoneally (i.p.). The administration of l-arginine significantly decreased the frequency of epileptiform activity while administration of l-NAME did not influence the mean frequency of epileptiform activity. Injection of 7-NI decreased the mean frequency of epileptiform activity but did not influence amplitude. Ascorbic acid decreased both the mean frequency and amplitude of penicillin-induced epileptiform activity in rats. The application of l-NAME partially and temporarily reversed the anticonvulsant effects of ascorbic acid. The results support the hypothesis of neuro-protective role for NO and ascorbic acid. The protective effect of ascorbic acid against epileptiform activity was partially and temporarily reversed by nonspecific nitric oxide synthase inhibitor l-NAME, but not selective neuronal nitric oxide synthase inhibitor 7-NI, indicating that ascorbic acid needs endothelial-NOS/NO route to decrease penicillin-induced epileptiform activity.

Vitamin C supplementation reconstitutes polyfunctional T cells in streptozotocin-induced diabetic rats

“…Male rats in the control group (n = 10) were injected with the vehicle alone (0.01 M citrate buffer, pH 4.5). The animals were divided into three experimental groups: group 1, control nondiabetic rats; group 2, diabetic rats; and group 3, diabetic rats orally supplemented with vitamin C (100 mg/kg body weight/day) [23] for 2 months. Blood glucose levels were measured 4 days after STZ injection by cutting off the tip of the tail, squeezing it gently and using OneTouch Ultra (LifeScan, Paris, France).…”

The involvement of neuronal nitric oxide synthase in antiepileptic action of alpha-asarone on pentylenetetrazol molding rats

“…NO was suggested to be an endogenous anticonvulsant in previous report [19], while others suggest a proconvulsant role for NO [20,21]. Mehmet et al [22] reported that L-NAME (100 mg/kg) did not affect both of the frequency and amplitude of penicillin induced epileptiform discharge in rats. It was suggested that L-NAME was able to weaken the beneficial action of some conventional anticonvulsive drugs [23].…”

The effects of treadmill exercise on penicillin-induced epileptiform activity

“…The soft tissue on the skull was removed and the bregma (reference point) was identified. Under stereotaxic guidance, two stainless steel screws were placed over the left somatomotor cortex (first screw 3 mm lateral and 4 mm rostral to bregma; second screw 3 mm lateral and 4 mm caudal to bregma) and a well conductor bipolar electrode was connected to the screws [ 19 , 20 ]. After observing the brain's basal activity with the PowerLab data acquisition system, a 1 mm hole was opened (1.5 mm left lateral and 1.5 mm caudal to the bregma) with a hand drill for injection of penicillin G potassium (Sigma Chemical Co., St. Louis, MO, USA), which was dissolved in sterile physiological saline.…”