Methylene blue protects against pentylenetetrazole-induced seizures, oxidative stress, and neuronal injury

Abstract

Methylene blue (MethyB) was shown to protect against different brain pathologies. In this study, the effect of acute administration of MethyB on epileptic seizures, brain oxidative stress, and neuronal injury induced in rats by pentylenetetrazole (PTZ) was studied. Rats received repeated intraperitoneal (i.p.) injections of PTZ until the development of status epilepticus and were i.p. treated once with MethyB at doses of 50 or 100 mg/kg, 30 min prior to the first PTZ injection. Results indicated that compared with the PTZ control group, the administration of MethyB at 50 and 100 mg/kg decreased the mean seizure score over the study period by 48.8% and 55.1%, respectively. The development of myoclonic jerks and generalized tonic-clonic seizures was inhibited by 90.0–85.0% and 45.4–56.3%, respectively, compared with the PTZ control group. The mean latency to develop status epilepticus increased by 43.1% after treatment with MethyB at 100 mg/kg. MethyB had no significant effect on the mean threshold dose of PTZ required to reach status epilepticus. MethyB showed inhibitory effects on the increase in brain lipid peroxidation (malondialdehyde), and nitric oxide induced PTZ by 16.7–24.0% and 25.2–32.6%, respectively. Meanwhile, the decrease in reduced glutathione and paraoxonase-1 (PON-1) activity and the increase in nuclear factor-kappa B (NF-κB) in the brain of PTZ-treated rats were attenuated by MethyB. Brain acetylcholinesterase (AChE) concentration decreased by PTZ and showed further decrements after treatment with either dose of MethyB. PTZ caused neuronal atrophy in the hippocampus and cerebral cortex and decreased neuronal size and number in the substantia nigra. These pathological changes were prevented by MethyB given at 100 mg/kg. These data indicate that treatment with MethyB inhibits the PTZ-induced seizures in rats and increases the latency to develop status epilepticus. In addition, MethyB decreases brain oxidative stress and protects against neuronal atrophy in this experimental model of generalized epilepsy.