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Apoptotic inducement of neuronal cells by codeine: possible role of disrupted redox state and caspase 3 signaling
BACKGROUND: Codeine, a common drug of abuse, has been reported to induce organ damage; however, there are scanty available data on the effects of codeine on the brain. OBJECTIVE: Thus, we tested the hypothesis that redox dysregulation and inflammation of the brain induced by codeine exposure is 8-OH...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278432/ https://www.ncbi.nlm.nih.gov/pubmed/34286140 http://dx.doi.org/10.1016/j.heliyon.2021.e07481 |
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author | Ajayi, A.F. Akhigbe, R.E. |
author_facet | Ajayi, A.F. Akhigbe, R.E. |
author_sort | Ajayi, A.F. |
collection | PubMed |
description | BACKGROUND: Codeine, a common drug of abuse, has been reported to induce organ damage; however, there are scanty available data on the effects of codeine on the brain. OBJECTIVE: Thus, we tested the hypothesis that redox dysregulation and inflammation of the brain induced by codeine exposure is 8-OHdG and/or caspase 3-dependent. METHODS: New Zealand White rabbits (Oryctolagus cuniculus) received vehicle (control; n = 7), low-dose codeine (4 mg/kg/day p.o; n = 6), or high-dose codeine (10 mg/kg/day p.o; n = 6) for six weeks. Body weight was checked before and after the study. RESULTS: Findings showed that codeine exposure resulted in redox dysregulation (evident by elevated MDA and H(2)O(2) accompanied by reduced enzymatic antioxidant activities), elevated MPO activity, and distorted cytoarchitecture of the brain tissue. The observed codeine-induced redox imbalance and brain inflammation was accompanied by depletion of neuronal and purkinje cells, reduced AchE activity, and elevated 8-OHdG levels and caspase 3 activity. CONCLUSIONS: The current study demonstrates that chronic codeine use induces oxido-inflammatory response and apoptosis of the brain tissue that is associated with neuronal and purkinje cells injury, and impaired AchE activity through 8-OHdG and/or caspase 3-dependent pathway. |
format | Online Article Text |
id | pubmed-8278432 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-82784322021-07-19 Apoptotic inducement of neuronal cells by codeine: possible role of disrupted redox state and caspase 3 signaling Ajayi, A.F. Akhigbe, R.E. Heliyon Research Article BACKGROUND: Codeine, a common drug of abuse, has been reported to induce organ damage; however, there are scanty available data on the effects of codeine on the brain. OBJECTIVE: Thus, we tested the hypothesis that redox dysregulation and inflammation of the brain induced by codeine exposure is 8-OHdG and/or caspase 3-dependent. METHODS: New Zealand White rabbits (Oryctolagus cuniculus) received vehicle (control; n = 7), low-dose codeine (4 mg/kg/day p.o; n = 6), or high-dose codeine (10 mg/kg/day p.o; n = 6) for six weeks. Body weight was checked before and after the study. RESULTS: Findings showed that codeine exposure resulted in redox dysregulation (evident by elevated MDA and H(2)O(2) accompanied by reduced enzymatic antioxidant activities), elevated MPO activity, and distorted cytoarchitecture of the brain tissue. The observed codeine-induced redox imbalance and brain inflammation was accompanied by depletion of neuronal and purkinje cells, reduced AchE activity, and elevated 8-OHdG levels and caspase 3 activity. CONCLUSIONS: The current study demonstrates that chronic codeine use induces oxido-inflammatory response and apoptosis of the brain tissue that is associated with neuronal and purkinje cells injury, and impaired AchE activity through 8-OHdG and/or caspase 3-dependent pathway. Elsevier 2021-07-03 /pmc/articles/PMC8278432/ /pubmed/34286140 http://dx.doi.org/10.1016/j.heliyon.2021.e07481 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Ajayi, A.F. Akhigbe, R.E. Apoptotic inducement of neuronal cells by codeine: possible role of disrupted redox state and caspase 3 signaling |
title | Apoptotic inducement of neuronal cells by codeine: possible role of disrupted redox state and caspase 3 signaling |
title_full | Apoptotic inducement of neuronal cells by codeine: possible role of disrupted redox state and caspase 3 signaling |
title_fullStr | Apoptotic inducement of neuronal cells by codeine: possible role of disrupted redox state and caspase 3 signaling |
title_full_unstemmed | Apoptotic inducement of neuronal cells by codeine: possible role of disrupted redox state and caspase 3 signaling |
title_short | Apoptotic inducement of neuronal cells by codeine: possible role of disrupted redox state and caspase 3 signaling |
title_sort | apoptotic inducement of neuronal cells by codeine: possible role of disrupted redox state and caspase 3 signaling |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278432/ https://www.ncbi.nlm.nih.gov/pubmed/34286140 http://dx.doi.org/10.1016/j.heliyon.2021.e07481 |
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