A hydrogen sulfide donor suppresses pentylenetetrazol-induced seizures in rats via PKC signaling

Zhu, Ziting; He, Yan; Liu, Zhongrui; Zhang, Wenlong; Kang, Qiyun; Lin, Yuwan; Qiu, Jingjun; Zhang, Yilong; Xu, Pingyi; Zhu, Xiaodong

doi:10.1016/j.ejphar.2021.173959

Cited by 9 publications

(7 citation statements)

References 47 publications

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“…Hydrogen sulfide has been identified as an important endogenous gasotransmitter regulating various physiological and pathological processes. Recently, we synthesized a novel more stable H 2 S donor, and found it has inhibitory effects on epileptic seizures in a pentetrazol (PTZ)-induced rat model ( Zhu et al, 2020 , 2021 ). The present study indicated that the novel H 2 S donor also reduced seizures in pilocarpine-induced mice model.…”

Section: Discussionmentioning

confidence: 99%

“…Hippocampus EEG was recorded as previously described ( Zhu et al, 2021 ). First, the mice were anesthetized by intraperitoneal injection of 2% sodium pentobarbital (30 mg/kg) and fixed in the stereotactic apparatus.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, we synthesized a novel carbazole-based H 2 S donor, which is safer and has more effective pharmacological administration to release H 2 S ( Li et al, 2008 ; Li Y. F. et al, 2009 ; Yang et al, 2020 ; Zhu et al, 2020 ). We found that the novel H 2 S donor has the effects of neuroprotection and reduction of epileptic seizures ( Zhu et al, 2020 , 2021 ; Liu et al, 2021 ). However, the underlying mechanisms of the H 2 S donor against seizures are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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A Novel Hydrogen Sulfide Donor Reduces Pilocarpine-Induced Status Epilepticus and Regulates Microglial Inflammatory Profile

Liu

Zhu

et al. 2021

Front. Cell. Neurosci.

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Although epilepsy is one of the most common neurologic disorders, there is still a lack of effective therapeutic drugs for it. Recently, we synthesized a novel hydrogen sulfide (H2S) donor, which is found to reduce seizures in animal models effectively. But it remains to be determined for its mechanism. In the present study, we found that the novel H2S donor could reduce pilocarpine-induced seizures in mice. It alleviated the epileptic behavior, the hippocampal electroencephalography (EEG) activity of seizures, and the damage of hippocampal neurons in status epilepticus mice. In addition, the novel H2S donor could reduce microglial inflammatory response. It not only reduced the upregulation of pro-inflammatory markers [inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2)] in status epilepticus mice, but also increased the levels of microglial anti-inflammatory marker arginase-1 (Arg-1). In lipopolysaccharide-treated microglia BV2 cells, administration of the H2S donor also significantly reduced the lipopolysaccharide-induced upregulation of the expression of the pro-inflammatory markers and increased the expression of the anti-inflammatory markers. Thus, the novel H2S donor regulates microglial inflammatory profile in status epilepticus mice and in vitro. These results suggested that the novel H2S donor can reduce seizures and regulate microglial inflammatory profile, which may be a novel mechanism and potential therapeutic strategy of the H2S donor anti-seizures.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Novel Hydrogen Sulfide Donor Reduces Pilocarpine-Induced Status Epilepticus and Regulates Microglial Inflammatory Profile

Liu

Zhu

et al. 2021

Front. Cell. Neurosci.

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“… Carbazole-based H 2 S donor (500 µM) injected into the lateral ventricle, 1 h after PTZ administration. [ 64 ] Diallyl disulphide (DAD) and diallyl trisulfide (DAT) GBM Human T98G cells Human U87 cells DAD (100 µM) for 24 h. DAT (25 µM) for 24 h. [ 59 ] Ectopic glioblastoma Induction in NOD.CB17-prkdcscid/J mice by subcutaneous implantation of U87MG cells. DAT (10ug/kg, 100ug/kg, and 10 mg/kg) 7 daily oral treatments for 4 weeks.…”

Section: Challenges In H 2 S Delivery To the Nervo...mentioning

confidence: 99%

Hydrogen Sulphide-Based Therapeutics for Neurological Conditions: Perspectives and Challenges

et al. 2023

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Central nervous system (CNS)-related conditions are currently the leading cause of disability worldwide, posing a significant burden to health systems, individuals and their families. Although the molecular mechanisms implicated in these disorders may be varied, neurological conditions have been increasingly associated with inflammation and/or impaired oxidative response leading to further neural cell damages. Therefore, therapeutic approaches targeting these defective molecular mechanisms have been vastly explored. Hydrogen sulphide (H2S) has emerged as a modulator of both inflammation and oxidative stress with a neuroprotective role, therefore, has gained interest in the treatment of neurological disorders. H2S, produced by endogenous sources, is maintained at low levels in the CNS. However, defects in the biosynthetic and catabolic routes for H2S metabolism have been identified in CNS-related disorders. Approaches to restore H2S availability using H2S-donating compounds have been recently explored in many models of neurological conditions. Nonetheless, we still need to elucidate the potential for these compounds not only to ameliorate defective biological routes, but also to better comprehend the implications on H2S delivery, dosage regimes and feasibility to successfully target CNS tissues. Here, we highlight the molecular mechanisms of H2S-dependent restoration of neurological functions in different models of CNS disease whilst summarising current administration approaches for these H2S-based compounds. We also address existing barriers in H2S donor delivery by showcasing current advances in mediating these constrains through novel biomaterial-based carriers for H2S donors.

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“…Hydrogen sulfide (H 2 S) is endogenously synthesized in mammals and is known to regulate a variety of physiological and pathological processes (Kimura, 2021 ). Zhu et al ( 2021 ) lab synthesized a novel H 2 S donor which is safer than traditional H 2 S donors and is able to release H 2 S effectively in the brain where it exhibits neuroprotective effects against epileptic seizures. To determine its mechanism, they investigated microglial inflammatory profiles associated with this H 2 S donor and found that it reduced seizures by downregulating pro-inflammatory profile while simultaneously increasing anti-inflammatory profile of microglia in pilocarpine-induced status epilepticus mice.…”

mentioning

confidence: 99%

Editorial: Modulation of neuronal excitability by non-neuronal cells in physiological and pathophysiological conditions

Chen

Peng

Zhu

et al. 2023

Front. Cell. Neurosci.

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A hydrogen sulfide donor suppresses pentylenetetrazol-induced seizures in rats via PKC signaling

Cited by 9 publications

References 47 publications

A Novel Hydrogen Sulfide Donor Reduces Pilocarpine-Induced Status Epilepticus and Regulates Microglial Inflammatory Profile

A Novel Hydrogen Sulfide Donor Reduces Pilocarpine-Induced Status Epilepticus and Regulates Microglial Inflammatory Profile

Hydrogen Sulphide-Based Therapeutics for Neurological Conditions: Perspectives and Challenges

Editorial: Modulation of neuronal excitability by non-neuronal cells in physiological and pathophysiological conditions

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