The Effects of Proton Pump Inhibitors (Pantoprazole) on Pentylenetetrazole-Induced Epileptic Seizures in Rats and Neurotoxicity in the SH-SY5Y Human Neuroblastoma Cell Line

2021

Chem. Pharm. Bull.

Thiamine (vitamin B1), which is synthesized only in bacteria, fungi and plants and which humans should take with diet, participates in basic biochemical and physiological processes in a versatile way and its deficiency is associated with neurological problems accompanied by cognitive dysfunctions. The rat glioblastoma (C6) model was used, which was exposed to a limited environment and toxicity with glutamate. The cells were stressed by exposure to glutamate in the presence and absence of thiamine. The difference in cell proliferation was evaluated in the XTT assay. Oxidative stress (OS) markers malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels, as well as endoplasmic reticulum (ER) stress markers 78-kDa glucose-regulated protein (GRP78), activating transcription factor-4 (ATF-4), and C/EBP homologous protein (CHOP) levels, were measured with commercial kits. Apoptosis determined by flow cytometry was confirmed by 4′,6-diamidino-2-phenylindole (DAPI) staining. At all concentrations, thiamine protects the cells and increased the viability against glutamate-induced toxicity. Thiamine also significantly decreased the levels of MDA, while increasing SOD and CAT levels. Moreover, thiamine reduced ER stress proteins' levels. Moreover, it lessened the apoptotic cell amount and enhanced the live-cell percentage in the flow cytometry and DAPI staining. As a result, thiamine may be beneficial nutritional support for individuals with a predisposition to neurodegenerative disorders due to its protective effect on glutamate cytotoxicity in glioblastoma cells by suppressing OS and ER stress.

Section: Methodsmentioning

confidence: 99%

Thiamine Protects Glioblastoma Cells against Glutamate Toxicity by Suppressing Oxidative/Endoplasmic Reticulum Stress

Ergül

2021

Chem. Pharm. Bull.

“…The cells were then treated with sCT (3 and 50 µg/mL), glutamate (10 mM), or their combinations and incubated for 24 hours. After incubation, the annexin V assay was performed according to the report in our previous study (Taskiran et al 2020).…”

Section: Annexin V Binding Assaymentioning

confidence: 99%

The effect of salmon calcitonin against glutamate-induced cytotoxicity in the C6 cell line and the roles the inflammatory and nitric oxide pathways play

Ergül

2021

Metab Brain Dis

Self Cite

Recent evidence has shown that salmon calcitonin (sCT) has positive effects on the nervous system.However, its effect and mechanisms on glutamate-induced cytotoxicity are still unclear. The current experiment was designed to examine the effect of sCT on glutamate-induced cytotoxicity in C6 cells, involving the in ammatory and nitric oxide stress pathways. The study used the C6 glioma cell line. Four cell groups were prepared to evaluate the effect of sCT on glutamate-induced cytotoxicity. The control group was without any treatment. Cells in the glutamate group were treated with 10 mM glutamate for 24 h. Cells in the sCT group were treated with various concentrations (3, 6, 12, 25, and 50 µg/mL) of sCT for 24 hours. Cells in the sCT + glutamate group were pre-treated with various concentrations of sCT for 1 hour and then exposed to glutamate for 24 hours. The cell viability was evaluated with an XTT assay. Nuclear factor kappa b (NF-kB), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), neuronal nitric oxide synthase (nNOS), nitric oxide (NO), cyclic guanosine monophosphate (cGMP), caspase-3, and caspase-9 levels in the cells were measured by ELISA kits. Apoptosis was detected by ow cytometry method. sCT at all concentrations signi cantly improved the cell viability in C6 cells after glutamateinduced cytotoxicity (p < 0.001). Moreover, sCT signi cantly reduced the levels of NF-kB (p < 0.001), TNFα, and IL-6 levels (p < 0.001). sCT also decreased nNOS, NO, and cGMP levels (P < 0.001). Furthermore, it decreased the apoptosis rate and increased the live-cell rate in the ow cytometry (P < 0.001). In conclusion, sCT has protective effects on glutamate-induced cytotoxicity in C6 glial cells by inhibiting in ammatory and nitric oxide pathways. sCT could be a useful supportive agent for people with neurodegenerative symptoms.

“…A mechanical homogenizer (Analytic Jena speed mill plus, Jena, Germany) was used to homogenize the tissue samples. The homogenates were centrifuged at 4000 rpm at 4ºC for 10 minutes as previously described (Taskiran et al 2020). The supernatants were obtained from the biochemical analysis and total protein levels were determined using the Bradford protein assay kit (Merck, Germany) (Kruger 2009).…”

Section: Preparation Of Brain Tissue Homogenatesmentioning

confidence: 99%

“…When there are adequate quantities of oxidants in the medium, ferrous ion is oxidized to ferric ion, which was measured to obtain TOS levels using xylenol orange. The method using the present study to measure levels of TNF-α, IL-1 β, nNOS, NO, sGC, cGMP, caspase-3, and caspase-9 in the cortex and hippocampus was described in our previous study (Taskiran et al 2020). TNF-α, IL-1 β, nNOS, NO, sGC, cGMP, caspase-3, and caspase-9 levels in the cortical and hippocampal supernatants were measured using rat ELISA commercial kits (BT Lab, Shanghai, China) following the manufacturer's instructions.…”

Section: Measurement Of Tas and Tosmentioning

confidence: 99%

The Effects And Possible Mechanisms of Vortioxetine on Pentylenetetrazole-Induced Seizures In Rats

Filiz

2021

Preprint

Self Cite

Antidepressants are known to demonstrate various effects on the nervous system. As a new antidepressant, vortioxetine is used for major depression in adult patients, with no clear indication of epileptic seizures. Therefore, the aim here was to examine the impact of vortioxetine on pentylenetetrazole-induced epileptic seizures in rats. The rats were randomly divided into 5 groups, each with 6 rats. Group 1 was control, Group 2 was administered saline (1 mL/kg/day serum physiologic), Group 3 was given (1 mg/kg/day diazepam), and Groups 4 and 5 were administered vortioxetine (2.5 and 5 mg/kg/day). The experimental groups (Groups 2-5) were given the drugs for a total of 7 days. Pentylenetetrazole (45 mg/kg) was administered on day 7 to all but the control group. Behavioral testing was performed using the passive avoidance and open field tasks. Total antioxidant status (TAS), total oxidant status (TOS), tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1 β), neuronal nitric oxide synthase (nNOS), nitric oxide (NO), soluble guanylate cyclase (sGC), cyclic guanosine monophosphate (cGMP) caspase-3, and caspase-9 levels were measured using a commercial kit. The groups receiving vortioxetine (2.5 mg/kg and 5 mg/kg) were found to have delayed epileptic seizure onset times and reduced seizure stages with improved memory impairment after seizures. These groups also had increased TAS levels and decreased TOS levels in the cortex and hippocampus. Additionally, TNF-α, IL-1 β, nNOS, sGC, cGMP, caspase-3, and caspase-9 levels in the cortex and hippocampus were statistically significantly lower for these groups. Vortioxetine was determined to have protective effects on pentylenetetrazole-induced seizures in rats, with alleviated seizures and improved memory impairment, oxidative stress, inflammation, and apoptosis. The mechanisms of vortioxetine may involve the inhibition of oxidative stress, inflammation, and the nNOS/sGC/cGMP signalling pathway.