The Impact of the Combined Administration of 1MeTIQ and MK-801 on Cell Viability, Oxidative Stress Markers, and Glutamate Release in the Rat Hippocampus
| Autor: | Magdalena Białoń, Danuta Jantas, Marcelina Żarnowska, Agnieszka Wąsik |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Cell Survival Cytotoxicity Glutathione reductase Excitotoxicity Glutamic Acid Pharmacology Toxicology medicine.disease_cause Hippocampus Neuroprotection Rats Sprague-Dawley Superoxide dismutase medicine Animals 1-Methyl-1 2 3 4-tetrahydroisoquinoline (1MeTIQ) Viability assay chemistry.chemical_classification MK-801 L-Lactate Dehydrogenase biology Superoxide Dismutase Chemistry General Neuroscience Glutathione peroxidase Glutamate receptor Catalase Isoquinolines Rats Oxidative Stress Glutathione Reductase biology.protein NMDA receptor Original Article Antioxidant enzymes Glutamate release Dizocilpine Maleate |
| Zdroj: | Neurotoxicity Research |
| ISSN: | 1476-3524 1029-8428 |
| Popis: | MK-801, as an N-methyl-D-aspartate (NMDA) receptor inhibitor, causes elevation in glutamate release, which may lead to an increase in excitotoxicity, oxidative stress and, consequently, cell death. 1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) shows antioxidant activity. The aim of the present study was to evaluate the effect of combined treatment with 1MeTIQ and MK-801 on cell viability, antioxidant enzyme activity, and glutamate release in the rat hippocampus. Cytotoxicity was measured using lactate dehydrogenase leakage assay (LDH) and the methyl tetrazolium (MTT) assay; antioxidant enzyme activity (glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT)) were measured by ELISA kits. The release of glutamate in the rat hippocampus was measured using in vivo microdialysis methodology. An in vitro study showed that MK-801 induced cell death in a concentration-dependent manner and that 1MeTIQ partially reduced this adverse effect of MK-801. An ex vivo study indicated that MK-801 produced an increase in antioxidant enzyme activity (GPx, GR, and SOD), whereas coadministration of MK-801 and 1MeTIQ restored the activity of these enzymes to the control level. An in vivo microdialysis study demonstrated that combined treatment with both drugs decreased the release of glutamate in the rat hippocampus. The above results revealed that 1MeTIQ shows limited neuroprotective activity under conditions of glutamate-induced neurotoxicity. |
| Databáze: | OpenAIRE |
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