Antioxidant effects of nerolidol in mice hippocampus after open field test.

The aim of this study was to evaluate the neuroprotective effects of nerolidol in mice hippocampus against oxidative stress in neuronal cells compared to ascorbic acid (positive control) as well as evaluated the nerolidol sedative effects by open field test compared to diazepam (positive control). Thirty minutes prior to behavioral observation on open field test, mice were intraperitoneally treated with vehicle, nerolidol (25, 50 and 75 mg/kg), diazepam (1 mg/kg) or ascorbic acid (250 mg/kg). To clarify the action mechanism of of nerolidol on oxidative stress in animals subjected to the open field test, Western blot analysis of Mn-superoxide dismutase and catalase in mice hippocampus were performed. In nerolidol group, there was a significant decrease in lipid peroxidation and nitrite levels when compared to negative control (vehicle). However, a significant increase was observed in superoxide dismutase and catalase activities in this group when compared to the other groups. Vehicle, diazepam, ascorbic acid and nerolidol groups did not affected Mn-superoxide dismutase, catalase mRNA or protein levels. Our findings strongly support the hypothesis that oxidative stress occurs in hippocampus. Nerolidol showed sedative effects in animals subjected to the open field test. Oxidative process plays a crucial role on neuronal pathological consequence, and implies that antioxidant effects could be achieved using this sesquiterpene.

Anticonvulsant and antioxidant effects of cyano-carvone and its action on acetylcholinesterase activity in mice hippocampus.

The anticonvulsant effect of cyano-carvone, a monoterpene monocyclic, was investigated in epilepsy model induced by pilocarpine. Cyano-carvone at doses of 25, 50 or 75 mg/kg promoted a reduction of 16.7, 33 and 66.7%, respectively, against pilocarpine-induced seizures, and it was efficacious in increasing both the latency to first seizures and the survival percentage, resulting in 33.3, 67 and 91.7% of protection against death induced by seizures, respectively (P < 0.05). The reference drug atropine (25 mg/kg) also produced a significant protection (100%). Its monoterpene, at 25, 50 and 75 mg/kg, was also capable to increase the latency for installation of status epilepticus induced by pilocarpine, and presented a significant protection against lipid peroxidation and nitrite formation in mice hippocampus (P < 0.05). In addition, it was observed that the cyano-carvone pretreatment increased the acetylcholinesterase activity in mice hippocampus after pilocarpine-induced seizures. The present results clearly indicate the anticonvulsant ability of cyano-carvone, which can be, at least in part, explained by the increased activity of the acetylcholinesterase enzyme. Our data suggest that the action mechanism can also be due to a direct activation of the antioxidant enzymes that could be associated with a reduction observed in oxidative stress in mice hippocampus, probably involving an inhibition of free radical production.

Oxidative stress in rat striatum after pilocarpine-induced seizures is diminished by alpha-tocopherol.

Alpha-tocopherol has numerous nonenzymatic actions and is a powerful liposoluble antioxidant. The objective of the present study was to evaluate the neuroprotective effects of alpha-tocopherol in rats against oxidative stress caused by pilocarpine-induced seizures. Wistar rats were intraperitoneally treated with 0.9% saline (control group), alpha-tocopherol (200 mg/kg, alpha-tocopherol group), pilocarpine (400 mg/kg, pilocarpine group), or the combination of alpha-tocopherol (200 mg/kg) and pilocarpine (400 mg/kg, i.p.; alpha-tocopherol plus pilocarpine group). After the treatments, all groups were observed for 24 h. The superoxide dismutase (Mn-SOD) and catalase activities, lipid peroxidation and nitrite concentrations were measured using spectrophotometrically methods. To clarify the mechanism of alpha-tocopherol on oxidative stress in pilocarpine model, Western blot analysis of Mn-SOD and catalase in rat striatum were performed. In the pilocarpine group, rats showed a significant increase in lipid peroxidation and nitrite levels. However, there were no alterations on Mn-SOD activity. On the other hand, the catalase activity augmented in pilocarpine group. In the alpha-tocopherol and pilocarpine co-administered rats, antioxidant treatment significantly reduced the lipid peroxidation level and nitrite content and increased the Mn-SOD and catalase activities in rat striatum after seizures. Pilocarpine, alpha-tocopherol plus pilocarpine and alpha-tocopherol groups did not affect of the Mn-SOD and catalase mRNA or protein levels. Our findings strongly support the hypothesis that oxidative stress occurs in striatum during pilocarpine-induced seizures, indicating that brain damage induced by the oxidative process plays a crucial role in seizures pathogenic consequences, which implies that strong protective effect could be achieved using alpha-tocopherol.

Lipoic acid inhibits caspase-dependent and -independent cell death pathways and is neuroprotective against hippocampal damage after pilocarpine-induced seizures.

Alpha-lipoic acid has some neuroprotective properties, but this action has not been investigated in models of epilepsy. The aim of the present study was to investigate the protective efficacy of α-lipoic acid (lipoic acid) against pilocarpine-induced cell death through the caspase-dependent or -independent mitochondrial apoptotic pathways. Wistar rats were injected intraperitoneally with 0.9% saline (control group), pilocarpine (400 mg/kg, pilocarpine group) alone, or α-lipoic acid (20 mg/kg) in association with pilocarpine (400 mg/kg) 30 min before administration of α-lipoic acid. After the treatments all groups were observed for 24 h. Cell death was reduced in lipoic acid-treated rats. Cytosolic translocation of cytochrome c and subsequent activation of caspase-3 were reduced by lipoic acid treatment. AIF nuclear translocation and subsequent large-scale DNA fragmentation were also decreased in lipoic acid-treated rats. Our study suggests that lipoic acid inhibits both caspase-dependent and -independent apoptotic pathways and may be neuroprotective against hippocampal damage during pilocarpine-induced seizures.