Thymoquinone Attenuates Brain Injury via an Anti-oxidative Pathway in a Status Epilepticus Rat Model

Abstract

Aim: Status epilepticus (SE) results in the generation of reactive oxygen species (ROS), which contribute to seizure-induced brain injury. It is well known that oxidative stress plays a pivotal role in status epilepticus (SE). Thymoquinone (TQ) is a bioactive monomer extracted from black cumin (Nigella sativa) seed oil that has anti-inflammatory, anti-cancer, and antioxidant activity in various diseases. This study evaluated the protective effects of TQ on brain injury in a lithium-pilocarpine rat model of SE and investigated the underlying mechanism related to antioxidative pathway.

Methods: Electroencephalogram and Racine scale were used to value seizure severity. Passive-avoidance test was used to determine learning and memory function. Moreover, anti-oxidative activity of TQ was observed using Western blot and super oxide dismutase (SOD) activity assay.

Results: Latency to SE increased in the TQ-pretreated group compared with rats in the model group, while the total power was significantly lower. Seizure severity measured on the Racine scale was significantly lower in the TQ group compared with the model group. Results of behavioral experiments suggest that TQ may also have a protective effect on learning and memory function. Investigation of the protective mechanism of TQ showed that TQ-pretreatment significantly increased the expression of Nrf2, HO-1 proteins and SOD in the hippocampus.

Conclusion: These findings showed that TQ attenuated brain injury induced by SE via an anti-oxidative pathway.

Keywords: Nrf2; brain injury; oxidative stress; status epilepticus; thymoquinone.

Figure 1

Total power was significantly lower in the TQ group after pilocarpine administration than in the model group (A, B). Pre-SE EEG of control group (a), model group (b), and TQ group (c) rats; post-SE EEG of control group (d), model group (e), and TQ group (f) rats. The latency to SE in the TQ group was longer than that in model group. *model group vs. control group, p<0.05, ΔTQ group vs. model group, p<0.05.

Figure 2

Effect of TQ on the epileptic behavior of status epileptic rats. *model group vs. control group, p<0.05, ΔTQ group vs. model group, p<0.05.

Figure 3

Effect of TQ on the epileptic behavior of SE rats. Latent period of the step-through test. ^*model group vs. control group, p<0.05 Δ TQ group vs. model group, p<0.05.

Figure 4

TQ increased Nrf2, HO-1 and SOD inhibition rate in the cortex and hippocampus of SE rats. (A) Protein extracted from hippocampal and cortical tissues was assayed by western blotting. Nrf2, HO-1 expression in SE rat brains was significantly lower than in control group rats. TQ significantly downregulated the expression of Nrf2 and HO-1. (B) The inhibition rate of SOD. ^*Model group vs. control group; ΔTQ group vs. model group, p < 0.05.