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N-Acetyl cysteine ameliorates hyperglycemia-induced cardiomyocyte toxicity by improving mitochondrial energetics and enhancing endogenous Coenzyme Q(9/10) levels
The diabetic heart has been linked with reduced endogenous levels of coenzyme Q(9/10) (CoQ), an important antioxidant and component of the electron transport chain. Although CoQ has displayed cardioprotective potential in experimental models of diabetes, the impact of N-acetyl cysteine (NAC) on mito...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883304/ https://www.ncbi.nlm.nih.gov/pubmed/31799124 http://dx.doi.org/10.1016/j.toxrep.2019.11.004 |
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author | Dludla, Phiwayinkosi V. Orlando, Patrick Silvestri, Sonia Mazibuko-Mbeje, Sithandiwe E. Johnson, Rabia Marcheggiani, Fabio Cirilli, Ilenia Muller, Christo J.F. Louw, Johan Obonye, Nnini Nyawo, Thembeka Nkambule, Bongani B. Tiano, Luca |
author_facet | Dludla, Phiwayinkosi V. Orlando, Patrick Silvestri, Sonia Mazibuko-Mbeje, Sithandiwe E. Johnson, Rabia Marcheggiani, Fabio Cirilli, Ilenia Muller, Christo J.F. Louw, Johan Obonye, Nnini Nyawo, Thembeka Nkambule, Bongani B. Tiano, Luca |
author_sort | Dludla, Phiwayinkosi V. |
collection | PubMed |
description | The diabetic heart has been linked with reduced endogenous levels of coenzyme Q(9/10) (CoQ), an important antioxidant and component of the electron transport chain. Although CoQ has displayed cardioprotective potential in experimental models of diabetes, the impact of N-acetyl cysteine (NAC) on mitochondrial energetics and endogenous levels of CoQ remains to be clarified. To explore these effects, high glucose-exposed H9c2 cardiomyocytes were used as an experimental model of hyperglycemia-induced cardiac injury. The results showed that high glucose exposure caused an increased production of reactive oxygen species (ROS), which was associated with impaired mitochondrial energetics as confirmed by a reduction of maximal respiration rate and depleted ATP levels. These detrimental effects were consistent with significantly reduced endogenous CoQ levels and accelerated cell toxicity. Although metformin demonstrated similar effects on mitochondrial energetics and cell viability, NAC demonstrated a more pronounced effect in ameliorating cytosolic and mitochondrial ROS production. Interestingly, the ameliorative effects of NAC against hyperglycemia-induced injury were linked with its capability to enhance endogenous CoQ levels. Although such data are to be confirmed in other models, especially in vivo studies, the overall findings provide additional evidence on the therapeutic mechanisms by which NAC protects against diabetes-induced cardiac injury. |
format | Online Article Text |
id | pubmed-6883304 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-68833042019-12-03 N-Acetyl cysteine ameliorates hyperglycemia-induced cardiomyocyte toxicity by improving mitochondrial energetics and enhancing endogenous Coenzyme Q(9/10) levels Dludla, Phiwayinkosi V. Orlando, Patrick Silvestri, Sonia Mazibuko-Mbeje, Sithandiwe E. Johnson, Rabia Marcheggiani, Fabio Cirilli, Ilenia Muller, Christo J.F. Louw, Johan Obonye, Nnini Nyawo, Thembeka Nkambule, Bongani B. Tiano, Luca Toxicol Rep Article The diabetic heart has been linked with reduced endogenous levels of coenzyme Q(9/10) (CoQ), an important antioxidant and component of the electron transport chain. Although CoQ has displayed cardioprotective potential in experimental models of diabetes, the impact of N-acetyl cysteine (NAC) on mitochondrial energetics and endogenous levels of CoQ remains to be clarified. To explore these effects, high glucose-exposed H9c2 cardiomyocytes were used as an experimental model of hyperglycemia-induced cardiac injury. The results showed that high glucose exposure caused an increased production of reactive oxygen species (ROS), which was associated with impaired mitochondrial energetics as confirmed by a reduction of maximal respiration rate and depleted ATP levels. These detrimental effects were consistent with significantly reduced endogenous CoQ levels and accelerated cell toxicity. Although metformin demonstrated similar effects on mitochondrial energetics and cell viability, NAC demonstrated a more pronounced effect in ameliorating cytosolic and mitochondrial ROS production. Interestingly, the ameliorative effects of NAC against hyperglycemia-induced injury were linked with its capability to enhance endogenous CoQ levels. Although such data are to be confirmed in other models, especially in vivo studies, the overall findings provide additional evidence on the therapeutic mechanisms by which NAC protects against diabetes-induced cardiac injury. Elsevier 2019-11-05 /pmc/articles/PMC6883304/ /pubmed/31799124 http://dx.doi.org/10.1016/j.toxrep.2019.11.004 Text en © 2019 The Authors http://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 | Article Dludla, Phiwayinkosi V. Orlando, Patrick Silvestri, Sonia Mazibuko-Mbeje, Sithandiwe E. Johnson, Rabia Marcheggiani, Fabio Cirilli, Ilenia Muller, Christo J.F. Louw, Johan Obonye, Nnini Nyawo, Thembeka Nkambule, Bongani B. Tiano, Luca N-Acetyl cysteine ameliorates hyperglycemia-induced cardiomyocyte toxicity by improving mitochondrial energetics and enhancing endogenous Coenzyme Q(9/10) levels |
title | N-Acetyl cysteine ameliorates hyperglycemia-induced cardiomyocyte toxicity by improving mitochondrial energetics and enhancing endogenous Coenzyme Q(9/10) levels |
title_full | N-Acetyl cysteine ameliorates hyperglycemia-induced cardiomyocyte toxicity by improving mitochondrial energetics and enhancing endogenous Coenzyme Q(9/10) levels |
title_fullStr | N-Acetyl cysteine ameliorates hyperglycemia-induced cardiomyocyte toxicity by improving mitochondrial energetics and enhancing endogenous Coenzyme Q(9/10) levels |
title_full_unstemmed | N-Acetyl cysteine ameliorates hyperglycemia-induced cardiomyocyte toxicity by improving mitochondrial energetics and enhancing endogenous Coenzyme Q(9/10) levels |
title_short | N-Acetyl cysteine ameliorates hyperglycemia-induced cardiomyocyte toxicity by improving mitochondrial energetics and enhancing endogenous Coenzyme Q(9/10) levels |
title_sort | n-acetyl cysteine ameliorates hyperglycemia-induced cardiomyocyte toxicity by improving mitochondrial energetics and enhancing endogenous coenzyme q(9/10) levels |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883304/ https://www.ncbi.nlm.nih.gov/pubmed/31799124 http://dx.doi.org/10.1016/j.toxrep.2019.11.004 |
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