Effect of dimethyl fumarate on neuroinflammation and apoptosis in pentylenetetrazol kindling model in rats

Singh, Neha; Saha, Lekha; Kumari, Puja; Singh, Jagjit; Bhatia, Alka; Banerjee, Dibyajyoti; Chakrabarti, Amitava

doi:10.1016/j.brainresbull.2018.11.013

Cited by 57 publications

(41 citation statements)

References 54 publications

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“…In epileptic patients, the plasma levels of the pro‐inflammatory cytokine IL‐6 were higher in comparison with healthy humans and were further elevated following seizures (Liimatainen, Fallah, Kharazmi, Peltola, & Peltola, ; Peltola, Hurme, Miettinen, & Keränen, ). Similarly, the concentrations or expressions of nuclear factor κB (NF‐κB), IL‐6, IL‐1β and TNF‐α have been elevated in the hippocampi of seizure‐induced rats (Mansoor et al., ; Singh et al., ). Although the effect of sex steroids on the seizure‐induced cytokine response was not studied before, oestradiol treatment in mice was shown to suppress the pro‐inflammatory transcription factor NF‐κB‐induced genes and the levels of cytokines and chemokines, while anti‐oestrogen treatment inhibited these reductions (Evans, Eckert, Lai, Adelman, & Harnish, ).…”

Section: Discussionmentioning

confidence: 99%

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Oestrogen receptor ERα and ERβ agonists ameliorate oxidative brain injury and improve memory dysfunction in rats with an epileptic seizure

Koyuncuoğlu

Tamer

Erzik

et al. 2019

Experimental Physiology

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New Findings What is the central question of this study?Could different hormonally active substances, including oestrogen receptor (ER) agonists, protect against oxidative brain damage and memory impairment induced by a single epileptic seizure in rats? If so, which signalling mechanisms are involved in their anti‐inflammatory effects? What is the main finding and its importance?Chronic administration of oestrogen, progesterone, ER modulators/agonists or blockade of testosterone exhibited anti‐inflammatory and antioxidant actions on single seizure‐induced neuronal injury, while ER agonists additionally improved memory function and up‐regulated CREB signalling and hippocampal GABA(A)α1 receptor density, suggesting that ERα or ERβ receptor activation may be beneficial in protecting against seizure‐related oxidative brain injury and cognitive dysfunction. Abstract The susceptibility to epileptic seizures is dependent on sex as well as fluctuations in oestrogen levels, while exogenous oestrogen was shown to have no effect or to facilitate or to inhibit seizure activity. Oestrogen receptors (ERs) mediate antioxidant and anti‐inflammatory actions in several inflammatory models, but the involvement of ERs in seizure‐induced neuronal injury has not been evaluated previously. In order to assess the effects of resveratrol, progesterone, oestradiol (E2), an anti‐testosterone (cyproterone acetate; CPA), a selective ER modulator (tamoxifen; TMX) and ERα/ERβ agonists (propyl pyrazole triol (PPT), diarylpropionitrile (DPN)) on oxidative brain damage and memory impairment due to epileptic seizure, male Wistar rats (n = 120) received one of the treatment choices either in drinking water or intraperitoneally for 31 days, and epileptic seizure was induced on the 28th day by injection of a single‐dose of pentylenetetrazole (45 mg kg−1). The results demonstrate that chronic pretreatment with resveratrol, progesterone, E2, CPA or TMX suppressed most of the inflammatory parameters indicative of oxidative neuronal injury, while treatment with the ER agonists DPN or PPT were found to be even more effective in limiting the oxidative damage. Treatment with DPN resulted in the up‐regulation of cAMP response element‐binding protein (CREB) and brain‐derived neurotrophic factor (BDNF) expression, while PPT up‐regulated expression of CREB without affecting BDNF levels. Moreover, both ER agonists provided protection against seizure‐induced memory loss with a concomitant increase in hippocampal GABA(A)α1‐positive cells. In conclusion, ER agonists, and more specifically ERβ agonist, appear to provide maximum protection against seizure‐induced oxidative brain injury and associated memory dysfunction by up‐regulating the expression of CREB, BDNF and GABA(A)α1 receptors.

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Section: Discussionmentioning

confidence: 99%

“…Similarly, the concentrations or expressions of nuclear factor B (NF-B), IL-6, IL-1 and TNF-have been elevated in the hippocampi of seizure-induced rats (Mansoor et al, 2018;Singh et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Oestrogen receptor ERα and ERβ agonists ameliorate oxidative brain injury and improve memory dysfunction in rats with an epileptic seizure

Koyuncuoğlu

Tamer

Erzik

et al. 2019

Experimental Physiology

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“…Apoptosis refers to a form of cell death controlled by genes, regulates the development of the body and maintains the stability of the internal environment (Abeti et al, 2016;Chen et al, 2017;Gahl et al, 2016;Han et al, 2018). Studies have shown that neuronal apoptosis is a key event in the pathogenesis of epilepsy, cerebral ischemia and other diseases (Abiega et al, 2016;Dai et al, 2018;Li et al, 2017;Singh et al, 2019). In this work, the effect of high and low doses of PHT on the apoptosis of cells of the rat hippocampus and cerebellum was studied.…”

Section: Discussionmentioning

confidence: 98%

“…Studies have shown that neuronal apoptosis is a key event in the pathogenesis of epilepsy and can play a role in reducing brain damage after epilepsy by inhibiting apoptosis (Dai et al, 2018;Singh et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…Numerous studies have shown that PHT not only has antiepileptic properties but also may induce neuronal apoptosis and thus damage the nervous system (Kaushal et al, 2016). Long-term use or an overdose of PHT may cause irreversible cerebellar atrophy (Fang et al, 2016;Singh et al, 2019;Ye et al, 2018). Therefore, preventing neuronal apoptosis is essential for the treatment of epilepsy.…”

Section: Introductionmentioning

confidence: 99%

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Dl-3-n-butylphthalide inhibits phenytoin-induced neuronal apoptosis in rat hippocampus and cerebellum

Chen

Liu

Wang

et al. 2019

J. Integr. Neurosci.

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Rats were divided into six groups: sham/control, Dl-3-n-butylphthalide, P1 (low phenytoin, 100 mg/kg), P2 (high phenytoin, 200 mg/kg), NP1 (Dl-3-n-butylphthalide 80 mg/kg, phenytoin 100 mg/kg), NP2 (Dl-3-nbutylphthalide 80 mg/kg, phenytoin 200 mg/kg). Hematoxylin/eosin and Nissl staining showed that, compared to the sham/control group, the Dl-3-n-butylphthalide group had no obvious hippocampal and cerebellar neuron loss, but there was a significant neuron loss in the P1 and P2 groups (P < 0.05), which was more obvious in the P2 group (P < 0.05). The positive expression of Bax and Bcl-2 proteins in hippocampal and cerebellar neurons was not significantly different between sham and Dl-3-nbutylphthalide groups; however, compared to sham, Bax expression was significantly increased and Bcl-2 was significantly decreased in the hippocampal and cerebellar neurons of rats in both P1 and P2 groups (P < 0.05), being more obvious in the P2 group (P < 0.05). Furthermore, the administration of Dl-3-n-butylphthalide attenuated the deleterious effects of phenytoin (P < 0.05). Our results indicate that phenytoin causes apoptosis of hippocampal and cerebellar neurons in rats in a dose-dependent manner, with the effect of a higher dose being more obvious, whereas, Dl-3-n-butylphthalide inhibits the phenytoininduced apoptosis of neurons and has a neuroprotective role.

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Dimethyl Fumarate Ameliorates the Endometriosis Through Anti‐Inflammatory and Anti‐Proliferation Mechanisms In Vitro and In Vivo

Kim,

Park,

Kim

et al. 2024

Advanced Therapeutics

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Dimethyl fumarate is a widely known therapeutic agent with anti‐inflammatory properties for psoriasis and multiple sclerosis. Despite the current attempts to use dimethyl fumarate for treating various inflammatory diseases, its effects on endometriosis have not been previously reported. Endometriosis is a genital disease that causes various health problems in women, and treatment methods targeting the inflammatory environment are being attempted. Therefore, it is hypothesized that dimethyl fumarate has therapeutic effects on endometriosis through its anti‐inflammatory effects. Dimethyl fumarate exerted remarkable effects on cellular mechanisms, including reactive oxygen species production, activation of mitogen‑activated protein kinase signals, loss of mitochondrial function, and disruption of calcium ion homeostasis in the immortalized human ovarian endometrial stromal cells. In an endometriosis mouse model, dimethyl fumarate downregulated cell cycle‐related genes and induced inhibitory effects on endometriosis lesion growth. In particular, the immune cell population and expression of inflammatory cytokines such as IL‐1β, IL‐6, and IL‐10 are regulated by dimethyl fumarate. These results support its potential as a therapeutic agent to control the excessive inflammatory environment in patients with endometriosis. This study identifies for the first time that dimethyl fumarate, which is already in clinical use, can be used to treat endometriosis.

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Effect of dimethyl fumarate on neuroinflammation and apoptosis in pentylenetetrazol kindling model in rats

Cited by 57 publications

References 54 publications

Oestrogen receptor ERα and ERβ agonists ameliorate oxidative brain injury and improve memory dysfunction in rats with an epileptic seizure

Oestrogen receptor ERα and ERβ agonists ameliorate oxidative brain injury and improve memory dysfunction in rats with an epileptic seizure

Dl-3-n-butylphthalide inhibits phenytoin-induced neuronal apoptosis in rat hippocampus and cerebellum

Dimethyl Fumarate Ameliorates the Endometriosis Through Anti‐Inflammatory and Anti‐Proliferation Mechanisms In Vitro and In Vivo

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