The protective effect of hydroxylated fullerene pretreatment on pilocarpine-induced status epilepticus

Status epilepticus (SE) is a neurological emergency. The pathological hallmark of neuronal damage after epileptic seizures could be the chain reaction of oxygen free radicals. Hydroxylated fullerenes (HFs) are novel and effective free radical scavengers, which play an important role in various neurological diseases. However, whether they have a protective effect against epileptic seizures remains elusive. Our study explores the effect of pretreatment with HFs in different doses (0.5, 5, and 10 mg/kg) on SEmodels induced by pilocarpine (PILO). The results suggest that HFs have a protective effect on SE in a dose-dependent manner. HFs significantly reduce the incidence of SE, prolong the latency to SE, reduce the malondialdehyde (MDA) levels, and increase the glutathione (GSH) and superoxide dismutase (SOD) levels. In addition, HFs significantly raise the expression of B-cell lymphoma-2 (Bcl-2) and reduce the expression of Bcl-2-associated X protein (Bax). We found that expressions of nuclear NF-E2-related factor 2 (nNrf2), heme oxygenase-1 (HO-1) and NADPH: quinone oxidoreductase-1 (NQO1) were upregulated 24 h after the onset of SE, but the increase was not enough to combat oxidative stress damage, nor to attenuate lipid peroxidation and apoptosis. The expressions of these proteins in HFs pretreatment groups increased more significantly than those in the epilepsy (EP) group, which effectively reduced lipid peroxidation and apoptosis in the hippocampus. In summary, these findings highlight that HFs pretreatment has a protective effect against PILO-induced SE in rats. It may relieve oxidative stress damage by activating the Nrf2-ARE signaling pathway. It provides evidence that fullerene derivatives may have therapeutic potential for epileptic seizures.