Thymoquinone attenuates brain injury via an antioxidative pathway in a status epilepticus rat model

Abstract

Status epilepticus (SE) is a common, lifethreatening neurologic disorder characterized by acute, prolonged epileptic seizures. The incidence rate of SE is about 0.05 to 0.1% in the general population and 1.1 to 14% in the epileptic population. SE has a poor prognosis because seizures that cannot be terminated quickly result in irreversible brain injury. It is known that multiple factors are involved in the pathogenesis of brain injury induced by SE, one of which is oxidative stress [1][2]. The generation of excess free radicals and increase in lipid peroxidation that occur during SE damage brain tissue, therefore, antioxidants might be effective for treatment of SE [3][4][5].Thymoquinone (TQ), a bioactive monomer derived from black seed (Nigella sativa) oil, has significant antioxidant effects [6][7][8]. It has been shown to suppress oxidative stress and attenuate seizure activity and lower hippocampal neuronal loss in an epilepsy model and in children with refractory seizures [9][10][11]. We speculate that TQ alleviates the brain injury of SE by modulating oxidative stress. It is thought that the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a key defensive role against oxidative stress in epilepsy [12][13][14]. This study evaluated the protective effects of TQ on brain injury in a status epilepticus rat model, and the underlying mechanism related to antioxidative pathway using biochemistry techniques and behavioral and electrophysiological tests. Materials and methods THYMOQUINONE ATTENUATES BRAIN INJURY VIA AN ANTI-OXIDATIVE PATHWAY IN A STATUS EPILEPTICUS RAT MODEL AbstractAim: 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...

The role of thymoquinone as a potent antioxidant in ameliorating the neurotoxic effect of sodium arsenate in female rat

“…TQ crosses the blood brain barrier and exerts neuromodulatory activities. It has a neuroprotective effect and improves brain injuries resulting from Parkinson's disease [5] and status epilepticus [6]. It is also useful in the treatment of glial tumours by inducing apoptosis of glial tumour cells [7].…”

Thymoquinone reverses learning and memory impairments and brain tissue oxidative damage in hypothyroid juvenile rats

“…In addition, scientific findings show that TQ exerts a protective effect against pilocarpine-induced brain injury and it ameliorates brain damage through an antioxidant pathway in a status epilepticus rat model 31 . It has also been shown that TQ reduces lipid peroxidation in the hippocampal tissue of rats in a global cerebral ischemia-reperfusion injury model…”

Nigella sativa oil protected the hippocampus against Acetyl cholinesterase and oxidative dysfunctions-driven impaired working memory in rats

“…[12] Nigella sativa oil (NSO) being a natural antioxidant essential oil, [12,13] with proven neuro-protective efficacies, [12,13,15,18.38] was explored as a potent neuroprotective substance against DDVP neurotoxicity. And effectively, NSO intervention in this study was vital in preventing the out-burst of both ROS and NO productions in the hippocampus of the DDVP and/ or NSO exposed rats, an effect that could be supported by its previously reported antioxidant efficacy against models of neurotoxicity [12,13,19,[39][40][41] The antioxidant effects of NSO against DDVP we observed in this study as well as those reported in other neurotoxic models, [12,13] further strengthen the efficacy of NSO against OPinduced neurological deficits. [42,43] Co-administration of NSO with DDVP also revealed that NSO was able to preserve the cholinergic integrity of the hippocampus, by minimizing AChE deactivation induced by DDVP in the exposed rats.…”

“…All of the above effects of the Nigella sativa oil can be associated with its antioxidant capacities which prevent oxidative damages, a process implicated in the initiation of pathological processes in various neurological diseases. [19,[39][40][41][42] Therefore we conclude that interventional administration of NSO in this study had hippocampal neuroprotective functions against the effects of DDVP exposure, and that this predominantly occurred through the modulation of oxidative and neurogenic functions.…”