Ketamine Protects Against Pilocarpine-Induced Oxidative Stress and Metabolic Enzyme Disturbances During Epileptogenesis in the Epilepsy Model

The present study aims to investigate the effects of subanesthetic doses of ketamine on oxidative responses induced by pilocarpine during epileptogenesis. Mice were intraperitoneally (i.p) administered either with pilocarpine (100 mg/kg every 20 minutes untill the beginning of status epilepticus, i.p), or ketamine (3 injections of 10 mg/kg, i.p every 30 minutes), which was administered before or after the status epilepticus. At the end of the treatment, brains were collected to evaluate pilocarpine-induced oxidative stress status and protection afforded by ketamine. Pilocarpine induced an increase in lipid and protein oxidation and a decrease in antioxidant enzyme activities such as catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD). Pilocarpine also increased hydrogen peroxide (H2O2), superoxide anion (O-2(-)), free iron, ionizable calcium and nitric oxide (NO). By contrast, it decreased intracellular magnesium levels. In addition, pilocarpine increased lactate dehydrogenase (LDH), lipase and xanthine oxidase but decreased creatine kinase and acetylcholinesterase activities. Ketamine alone or in cotreatment with pilocarpine had either the reverse effect or prevented classical biological effects of pilocarpine. Interestingly, subanesthetic doses of ketamine prevent the effects of pilocarpine brain oxidative response in the epilepsy mouse model.