Neuroprotective effects of mirtazapine and imipramine and their effect in pro- and anti-apoptotic gene expression in human neuroblastoma cells
Autor: | Ana Lúcia S. Rodrigues, Nelson H. Gabilan, Vicente Lieberknecht, Daiane Fátima Engel |
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Rok vydání: | 2020 |
Předmět: |
Pharmacology
chemistry.chemical_classification Reactive oxygen species Programmed cell death Chemistry Mirtazapine General Medicine medicine.disease Neuroprotection Imipramine 03 medical and health sciences 0302 clinical medicine 030220 oncology & carcinogenesis Neuroblastoma medicine Antidepressant MTT assay 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Pharmacological Reports. 72:563-570 |
ISSN: | 2299-5684 1734-1140 |
DOI: | 10.1007/s43440-019-00009-w |
Popis: | Experimental and clinical studies indicate that neuronal death with the presence of high levels of reactive oxygen species are present in depressed patients and antidepressants might display neuroprotective effects against them. However, the mechanisms underlying antidepressant neuroprotection are not completely understood. In our previous study, we showed that mirtazapine modulated the expression of pro- and anti-apoptotic proteins in mouse brain structures, but there are no data in human cells. Thus, this work was designed to study the possible neuroprotective properties of mirtazapine and imipramine, two commercially available antidepressants with different primary mechanisms of action, in human neuroblastoma SH-SY5Y cells against an oxidative insult. SH-SY5Y cells were preincubated with mirtazapine and imipramine (1–20 μM) for 24 h, then hydrogen peroxide (H2O2) was added into the medium containing the antidepressants for additional 24 h, and MTT assay was carried out subsequently. Also, to elucidate the molecular mechanism underlying the neuroprotective properties of antidepressants, we investigated the effects of mirtazapine and imipramine (2 μM) in pro- and anti-apoptotic proteins gene expression in SH-SY5Y cells. Mirtazapine (1 and 2 μM) and imipramine (1and 2 μM) protected against hydrogen peroxide-induced cellular viability impairment. Most importantly, both compounds reduced p53 mRNA expression, but only imipramine enhanced the Bcl-2/Bax ratio. The obtained data indicate that mirtazapine and imipramine have neuroprotective effects against H2O2-induced cell death. Although both antidepressants reduced Bax and p53 mRNA expression, only the protection mediated by imipramine might be due to its ability to enhance Bcl-2/Bax ratio. |
Databáze: | OpenAIRE |
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