Ferulic acid ameliorates pentylenetetrazol-induced seizures by reducing neuron cell death

Abstract

To investigate the neuroprotective effect of ferulic acid (FA) in a pentylenetetrazol (PTZ)induced seizures rat model, the seizures behaviour, spatial learning ability and memory capability of the rats were assessed. Both the antioxidation and anti-apoptosis pathways were also investigated. In this study, male Wistar rats were randomly divided into 3 groups (n = 12 in each group). For 28 days, the rats were administered saline alone (i.p. normal saline, NS group), PTZ (40 mg/kg, i.p., PTZ group) once daily to induce seizures, or FA (i.p. 60 mg/kg) 20 min before being given PTZ (40 mg/kg, i.p., FA + PTZ group) to assess the neuroprotective effect of FA. The seizures behaviour of the rats was analysed with the Racine scale. The spatial learning and memory capacity of the rats were assessed by the Morris water maze test. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured, and both in situ staining with the DNA-binding bisbenzimide Hoechst 33258 and TUNEL assays were used to assess apoptosis. Western blotting was used to further analyse the expression of Apaf-1, caspase-9, caspase-3, Bcl-2, Bid, Bax, cleaved caspase-3 and cytochrome c. The results showed that compared to the those of the PTZ group, FA pre-treatment significantly (p < 0.01) reduced the Racine scores starting at day 4, prolonged the latency of the onset of seizure at day 28, reduced the escape latency period starting at day 2, increased the frequency of crossing the platform location, increased the SOD activity, reduced the MDA content and apoptosis rate, and upregulated the Bcl-2 levels whilst downregulating the Bax, cytochrome c, Apaf-1, caspase-9, caspase-3, cleaved caspase-3 and Bid expression levels. This study demonstrated that pre-treatment with FA exerts strong neuroprotective effects by reducing seizures behaviour and by improving spatial learning ability and memory capacity. The neuroprotective effect may be a result of a reduction in neuron cell death that occurs via the antioxidative and anti-apoptotic pathways.

Curcumin offsets PTZ-induced epilepsy: involving inhibition of apoptosis, wnt/β-catenin, and autophagy pathways

“…On the other hand, treatment with curcumin decreased significantly caspase-3 splitting in the hippocampus CA3 region suggesting that downregulation of caspase-3 might be a potential effect for the curcumin on PTZ-epileptic rat model. In agreement with these findings, Zhang et al [25], reported that FA in PTZ-kindled rat model caused significant decrease in apoptosis percentage with upregulation of antiapoptotic Bcl-2 protein levels and downregulation of the Bax, cytochrome c, Apaf-1, caspase-9, caspase-3, cleaved caspase-3, and Bid protein levels in brain tissues. Also, we investigated the expression of Wnt-β-catenin signaling pathway that plays a role in neurogenesis and differentiation of neuronal cells [32] in PTZ-induced epilepsy.…”

“…Also, the antioxidant effect of curcumin in PTZ-kindled rats demonstrated by Kaur et al [22]. Moreover, Zhang et al [25], reported that administration of ferulic acid (FA) at a dose of 60 mg/kg i.p. 20 min before PTZ injection (40 mg/kg) caused significant reduction the Racine scores, significant increase in the onset latency of seizure and frequency of crossing the platform location with significant reduction in oxidative stress in brain tissues (increase in superoxide dismutase (SOD) enzyme activity and decrease in MDA contents).…”

Apoptosis‑antagonizing transcription factor is involved in rat post‑traumatic epilepsy pathogenesis

“…These results strongly suggested the involvement of AATF in the neuronal apoptosis of PTE. Recent studies have reported that certain molecules or drugs can alleviate epilepsy by reducing neuronal apoptosis (28)(29)(30). For example, it has been found that ferulic acid ameliorates pentylenetetrazol-induced seizures through reducing neuron cell death (28).…”

“…Recent studies have reported that certain molecules or drugs can alleviate epilepsy by reducing neuronal apoptosis (28)(29)(30). For example, it has been found that ferulic acid ameliorates pentylenetetrazol-induced seizures through reducing neuron cell death (28). Furthermore, AATF was previously demonstrated to be involved in Alzheimer's disease, and could be considered a novel cytoprotective factor against apoptosis (18,31).…”

<p>microRNA-182 Negatively Influences the Neuroprotective Effect of Apelin Against Neuronal Injury in Epilepsy</p>

“…6,7 Furthermore, excitotoxicity, 6 ischemia/hypoxia, 8 oxidative stress, 1 and changes in blood-brain barrier function 9 contribute to the neuronal death in epilepsy. Reducing neuronal death could alleviate pentylenetetrazol (PTZ)- 10 and kainic acid-induced 11 seizures. Hence, protecting neurons from death is a potential target for epilepsy control and treatment.…”