scholarly journals Reductions in Hydrogen Sulfide Precede Onset of Mitochondrial Quality Control in the Corneal Kindled Mouse Model of Epilepsy

2021 ◽  
Author(s):  
Christi Cho ◽  
Maxwell Zeigler ◽  
Stephanie Mizuno ◽  
Richard S. Morrison ◽  
Rheem Totah ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Mouse Model ◽  
Membrane Integrity ◽  
Brain Homogenate ◽  
Maximal Electroshock ◽  
Maximal Electroshock Seizure ◽  
Mitochondrial Stress ◽  
Acute Seizures ◽  
Related Proteins

Epilepsy is a heterogenous neurological disorder characterized by recurrent unprovoked seizures, mitochondrial stress, and neurodegeneration. Hydrogen sulfide (H2S), a gasotransmitter, promotes mitochondrial function and biogenesis, elicits neuromodulation and neuroprotection, and may acutely suppress seizures. A major gap in knowledge remains in understanding the role of mitochondrial dysfunction and progressive changes in H2S levels following acute seizures and during epileptogenesis. We thus sought to quantify changes in H2S and its methylated metabolite (MeSH) via LC-MS/MS subsequent to acute maximal electroshock and 6 Hz 44 mA seizures in mice, as well as in the corneal kindled mouse model of chronic seizures. Plasma H2S was acutely reduced after a maximal electroshock seizure. H2S or MeSH levels in whole brain homogenate and expression of related genes in corneal kindled mice were not altered. However, plasma H2S and MeSH levels were significantly lower during kindling, but not after established kindling. Morever, we demonstrated a time-dependent increase in expression of mitochondrial membrane integrity-related proteins, Opa1, Mfn2, Drp1, and Mff during kindling, which did not correlate with gene expression. Taken together, short-term reductions in plasma H2S could be a novel biomarker for seizures. Future studies should further define the role of H2S and mitochondrial stress in epilepsy.

The Inhibitory Role of Hydrogen Sulfide in Airway Hyperresponsiveness and Inflammation in a Mouse Model of Asthma

2013 ◽  
Vol 182 (4) ◽  
pp. 1188-1195 ◽  
Author(s):  
Gensheng Zhang ◽  
Peipei Wang ◽  
Guangdong Yang ◽  
Qiuhui Cao ◽  
Rui Wang
Keyword(s):  
Hydrogen Sulfide ◽  
Mouse Model ◽  
Airway Hyperresponsiveness ◽  
Inhibitory Role

scholarly journals S(+)-(2E)-N-(2-Hydroxypropyl)-3-Phenylprop-2-Enamide (KM-568): A Novel Cinnamamide Derivative with Anticonvulsant Activity in Animal Models of Seizures and Epilepsy

2020 ◽  
Vol 21 (12) ◽  
pp. 4372
Author(s):  
Agnieszka Gunia-Krzyżak ◽  
Ewa Żesławska ◽  
Karolina Słoczyńska ◽  
Dorota Żelaszczyk ◽  
Aleksandra Sowa ◽  
...  
Keyword(s):  
Mouse Model ◽  
Anticonvulsant Activity ◽  
Treatment Options ◽  
Seizure Threshold ◽  
Base Substitution ◽  
Maximal Electroshock ◽  
Susceptible Mouse ◽  
Acute Seizures ◽  
Seizure Model

Epilepsy is one of the most frequent neurological disorders affecting about 1% of the world’s human population. Despite availability of multiple treatment options including antiseizure drugs, it is estimated that about 30% of seizures still remain resistant to pharmacotherapy. Searching for new antiseizure and antiepileptic agents constitutes an important issue within modern medicinal chemistry. Cinnamamide derivatives were identified in preclinical as well as clinical studies as important drug candidates for the treatment of epilepsy. The cinnamamide derivative presented here: S(+)-(2E)-N-(2-hydroxypropyl)-3-phenylprop-2-enamide (S(+)-N-(2-hydroxypropyl)cinnamamide, compound KM-568) showed anticonvulsant activity in several models of epilepsy and seizures in mice and rats. It was active in a genetic animal model of epilepsy (Frings audiogenic seizure-susceptible mouse model, ED50 = 13.21 mg/kg, i.p.), acute seizures induced electrically (maximal electroshock test ED50 = 44.46 mg/kg mice i.p., ED50 = 86.6 mg/kg mice p.o., ED50 = 27.58 mg/kg rats i.p., ED50 = 30.81 mg/kg rats p.o., 6-Hz psychomotor seizure model 32 mA ED50 = 71.55 mg/kg mice i.p., 44 mA ED50 = 114.4 mg/kg mice i.p.), chronic seizures induced electrically (corneal kindled mouse model ED50 = 79.17 mg/kg i.p., hippocampal kindled rat model ED50 = 24.21 mg/kg i.p., lamotrigine-resistant amygdala kindled seizure model in rats ED50 = 58.59 mg/kg i.p.), acute seizures induced chemically (subcutaneous metrazol seizure threshold test ED50 = 104.29 mg/kg mice i.p., ED50 = 107.27 mg/kg mice p.o., ED50 = 41.72 mg/kg rats i.p., seizures induced by picrotoxin in mice ED50 = 94.11 mg/kg i.p.) and the pilocarpine-induced status epilepticus model in rats (ED50 = 279.45 mg/kg i.p., ED97 = 498.2 mg/kg i.p.). The chemical structure of the compound including configuration of the chiral center was confirmed by NMR spectroscopy, LC/MS spectroscopy, elemental analysis, and crystallography. Compound KM-568 was identified as a moderately stable derivative in an in vitro mouse liver microsome system. According to the Ames microplate format mutagenicity assay performed, KM-568 was not a base substitution or frameshift mutagen. Cytotoxicity evaluation in two cell lines (HepG2 and H9c2) proved the safety of the compound in concentrations up to 100 µM. Based on the results of anticonvulsant activity and safety profile, S(+)-(2E)-N-(2-hydroxypropyl)-3-phenylprop-2-enamide could be proposed as a new lead compound for further preclinical studies on novel treatment options for epilepsy.

scholarly journals An Anticancer Role of Hydrogen Sulfide in Human Gastric Cancer Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Li Zhang ◽  
Qi Qi ◽  
Jianqiang Yang ◽  
Dongsheng Sun ◽  
Chunfeng Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Hydrogen Sulfide ◽  
Cancer Cells ◽  
Mammalian Cells ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Induced Apoptosis ◽  
Related Proteins

Hydrogen sulfide (H2S) can be synthesized in mammalian cells by cystathionineγ-lyase (CSE) and/or cystathionineβ-synthase (CBS). Both CSE and CBS are expressed in rat gastric tissues but their role in human gastric neoplasia has been unclear. The aims of the present study were to detect CSE and CBS proteins in human gastric cancer and determine the effect of exogenous NaHS on the proliferation of gastric cancer cells. We found that both CSE and CBS proteins were expressed in human gastric cancer cells and upregulated in human gastric carcinoma mucosa compared with those in noncancerous gastric samples. NaHS induced apoptosis of gastric cancer cells by regulating apoptosis related proteins. Also, NaHS inhibited cancer cell migration and invasion. An antigastric cancer role of H2S is thus indicated.

The role of tachykinin 1 in a mouse model of trait anxiety

2007 ◽  
Vol 40 (05) ◽  
Author(s):  
L Czibere ◽  
LA Baur-Jaronowski ◽  
P Weber ◽  
B Pütz ◽  
M Panhuysen ◽  
...  
Keyword(s):  
Mouse Model ◽  
Trait Anxiety

Are Viruses and Parasites Linked to Celiac Disease? A Question that Still has no Definite Answer

2019 ◽  
Vol 20 (14) ◽  
pp. 1181-1193 ◽  
Author(s):  
Aref Shariati ◽  
Hamid R. Aslani ◽  
Mohammad R.H. Shayesteh ◽  
Ali Taghipour ◽  
Ahmad Nasser ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Multiple Roles ◽  
Barr Virus ◽  
The People ◽  
Intestinal Infections ◽  
Inflammatory Bowel ◽  
Epstein Barr ◽  
Irritable Bowel ◽  
Related Proteins

Celiac Disease (CD) is a complex autoimmune enteropathy of the small intestine that commonly occurs in genetically predisposed individuals due to intake of gluten and related proteins. Gluten consumption, duration of breast-feeding, various infections, especially frequent intestinal infections, vaccinations and use of antibiotics can be linked to CD. It is predicted that it affects 1% of the global population and its incidence rate is increasing. Most of the people with the HLA-DQ2 or HLADQ8 are at a higher risk of developing this disease. The link between infections and autoimmune diseases has been very much considered in recent years. In several studies, we explained that pathogenic and non-pathogenic microorganisms might have multiple roles in initiation, exacerbation, and development of Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD). In various studies, the relationship between infections caused by viruses, such as Epstein-Barr Virus (EBV), Rotavirus, Hepatitis C (HCV), Hepatitis B virus (HBV), Cytomegalovirus (CMV), and Influenza virus, and parasites including Giardia spp. and Toxoplasma gondii with CD has been raised. However, increasing evidence proposes that some of these microorganisms, especially helminths, can also have protective and even therapeutic roles in the CD process. Therefore, in order to determine the role of microorganisms in the process of this disease, we attempted to summarize the evidence suggesting the role of viral and parasitic agents in pathogenesis of CD.

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