Glycyrrhizin ameliorates oxidative stress and inflammation in hippocampus and olfactory bulb in lithium/pilocarpine-induced status epilepticus in rats

Abstract

Glycyrrhizin (GL) is a triterpene present in the roots and rhizomes of Glycyrrhiza glabra that has anti-inflammatory, hepatoprotective and neuroprotective effects. Recently, it was demonstrated that GL produced neuroprotective effects on the postischemic brain as well as on the kainic acid injury model in rats. In addition to this, GL also prevented excitotoxic effects on primary cultures. The aims of the present study were to evaluate GL scavenging properties and to investigate GL’s effect on oxidative stress and inflammation in the lithium/pilocarpine-induced seizure model in two cerebral regions, hippocampus and olfactory bulb, at acute time intervals (3 or 24h) after status epilepticus (SE).Fluorometric methods showed that GL scavenged three reactive oxygen species: hydrogen peroxide, peroxyl radicals and superoxide anions. In contrast, GL was unable to scavenge peroxynitrite, hydroxyl radicals, singlet oxygen and 2,2-diphenil-1-picrylhydrazyl (DPPH) radicals suggesting that GL is a weak scavenger.Additionally, administration of GL (50mg/kg, i.p.) 30min before pilocarpine administration significantly suppressed oxidative stress. Moreover, malondialdehyde levels were diminished and glutathione levels were maintained at control values in both cerebral regions at 3 and 24 after SE. At 24h after SE, glutathione S-transferase and superoxide dismutase activity increased in the hippocampus, while both glutathione reductase and glutathione peroxidase activity were unchanged in the olfactory bulb at that time.In addition, GL suppressed the induction of the proinflammatory cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in both cerebral regions evaluated. These results suggest that GL confers protection against pilocarpine damage via antioxidant and anti-inflammatory effects.