Study of the potential toxicity of adrenaline to neurons, using the SH-SY5Y human cellular model
Abstract Prolonged overexposure to catecholamines causes toxicity, usually credited to continuous adrenoceptor stimulation, autoxidation, and the formation of reactive pro-oxidant species. Non-differentiated SH-SY5Y cells were used to study the possible contribution of oxidative stress in adrenaline...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Universidade de São Paulo
2023-05-01
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| Series: | Brazilian Journal of Pharmaceutical Sciences |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502023000100336&lng=en&tlng=en |
| _version_ | 1797830831505408000 |
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| author | Vera Marisa Costa João Paulo Capela Maria Lourdes Bastos Fernando Remião Kurt James Varner José Alberto Duarte Félix Carvalho |
| author_facet | Vera Marisa Costa João Paulo Capela Maria Lourdes Bastos Fernando Remião Kurt James Varner José Alberto Duarte Félix Carvalho |
| author_sort | Vera Marisa Costa |
| collection | DOAJ |
| description | Abstract Prolonged overexposure to catecholamines causes toxicity, usually credited to continuous adrenoceptor stimulation, autoxidation, and the formation of reactive pro-oxidant species. Non-differentiated SH-SY5Y cells were used to study the possible contribution of oxidative stress in adrenaline (ADR)-induced neurotoxicity, as a model to predict the toxicity of this catecholamine to peripheral nerves. Cells were exposed to several concentrations of ADR (0.1, 0.25, 0.5 and 1mM) and two cytotoxicity assays [lactate dehydrogenase (LDH) release and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction] were performed at several time-points (24, 48, and 96h). The cytotoxicity of ADR was concentration- and time-dependent in both assays, since the lowest concentration tested (0.1mM) also caused significant cytotoxicity at 96h. N-acetyl-cysteine (1mM), a precursor of glutathione synthesis, prevented ADR-induced toxicity elicited by 0.5mM and 0.25mM ADR following a 96-h exposure, while the antioxidant Tiron (100µM) was non-protective. In conclusion, ADR led to mitochondrial distress and ultimately cell death in non-differentiated SH-SY5Y cells, possibly because of ADR oxidation products. The involvement of such processes in the catecholamine-induced peripheral neuropathy requires further analysis. |
| first_indexed | 2024-04-09T13:42:23Z |
| format | Article |
| id | doaj.art-2e16d9635d4a4183998547ec2c62e21c |
| institution | Directory Open Access Journal |
| issn | 2175-9790 |
| language | English |
| last_indexed | 2024-04-09T13:42:23Z |
| publishDate | 2023-05-01 |
| publisher | Universidade de São Paulo |
| record_format | Article |
| series | Brazilian Journal of Pharmaceutical Sciences |
| spelling | doaj.art-2e16d9635d4a4183998547ec2c62e21c2023-05-09T07:33:20ZengUniversidade de São PauloBrazilian Journal of Pharmaceutical Sciences2175-97902023-05-015910.1590/s2175-97902023e20467Study of the potential toxicity of adrenaline to neurons, using the SH-SY5Y human cellular modelVera Marisa Costahttps://orcid.org/0000-0002-0471-2756João Paulo Capelahttps://orcid.org/0000-0003-2607-1264Maria Lourdes Bastoshttps://orcid.org/0000-0001-9895-503XFernando Remiãohttps://orcid.org/0000-0003-1382-5119Kurt James Varnerhttps://orcid.org/0000-0001-5460-8044José Alberto Duartehttps://orcid.org/0000-0003-4756-5917Félix Carvalhohttps://orcid.org/0000-0003-3858-3494Abstract Prolonged overexposure to catecholamines causes toxicity, usually credited to continuous adrenoceptor stimulation, autoxidation, and the formation of reactive pro-oxidant species. Non-differentiated SH-SY5Y cells were used to study the possible contribution of oxidative stress in adrenaline (ADR)-induced neurotoxicity, as a model to predict the toxicity of this catecholamine to peripheral nerves. Cells were exposed to several concentrations of ADR (0.1, 0.25, 0.5 and 1mM) and two cytotoxicity assays [lactate dehydrogenase (LDH) release and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction] were performed at several time-points (24, 48, and 96h). The cytotoxicity of ADR was concentration- and time-dependent in both assays, since the lowest concentration tested (0.1mM) also caused significant cytotoxicity at 96h. N-acetyl-cysteine (1mM), a precursor of glutathione synthesis, prevented ADR-induced toxicity elicited by 0.5mM and 0.25mM ADR following a 96-h exposure, while the antioxidant Tiron (100µM) was non-protective. In conclusion, ADR led to mitochondrial distress and ultimately cell death in non-differentiated SH-SY5Y cells, possibly because of ADR oxidation products. The involvement of such processes in the catecholamine-induced peripheral neuropathy requires further analysis.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502023000100336&lng=en&tlng=enNeurotoxicityAdrenalineN-acetyl-cysteineTironReactive species |
| spellingShingle | Vera Marisa Costa João Paulo Capela Maria Lourdes Bastos Fernando Remião Kurt James Varner José Alberto Duarte Félix Carvalho Study of the potential toxicity of adrenaline to neurons, using the SH-SY5Y human cellular model Brazilian Journal of Pharmaceutical Sciences Neurotoxicity Adrenaline N-acetyl-cysteine Tiron Reactive species |
| title | Study of the potential toxicity of adrenaline to neurons, using the SH-SY5Y human cellular model |
| title_full | Study of the potential toxicity of adrenaline to neurons, using the SH-SY5Y human cellular model |
| title_fullStr | Study of the potential toxicity of adrenaline to neurons, using the SH-SY5Y human cellular model |
| title_full_unstemmed | Study of the potential toxicity of adrenaline to neurons, using the SH-SY5Y human cellular model |
| title_short | Study of the potential toxicity of adrenaline to neurons, using the SH-SY5Y human cellular model |
| title_sort | study of the potential toxicity of adrenaline to neurons using the sh sy5y human cellular model |
| topic | Neurotoxicity Adrenaline N-acetyl-cysteine Tiron Reactive species |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502023000100336&lng=en&tlng=en |
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