Cytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative Analysis
Mitochondriotropic antioxidants (MC<sub>3</sub>, MC<sub>6.2</sub>, MC<sub>4</sub> and MC<sub>7.2</sub>) based on dietary antioxidants and analogs (caffeic, hydrocaffeic, trihydroxyphenylpropanoic and trihydroxycinnamic acids) were developed. In this st...
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2021
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oai:doaj.org-article:a860ae5232fb4fd5a4306babf39f38512021-11-25T16:52:44ZCytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative Analysis10.3390/biom111116052218-273Xhttps://doaj.org/article/a860ae5232fb4fd5a4306babf39f38512021-10-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1605https://doaj.org/toc/2218-273XMitochondriotropic antioxidants (MC<sub>3</sub>, MC<sub>6.2</sub>, MC<sub>4</sub> and MC<sub>7.2</sub>) based on dietary antioxidants and analogs (caffeic, hydrocaffeic, trihydroxyphenylpropanoic and trihydroxycinnamic acids) were developed. In this study, we evaluate and compare the cytotoxicity profile of novel mitochondria-targeted molecules (generally known as MitoCINs) on human HepG2 and differentiated SH-SY5Y cells with the quinone-based mitochondria-targeted antioxidants MitoQ and SkQ<sub>1</sub> and with two non-targeted antioxidants, resveratrol and coenzyme Q<sub>10</sub> (CoQ<sub>10</sub>). We further evaluate their effects on mitochondrial membrane potential, cellular oxygen consumption and extracellular acidification rates. Overall, MitoCINs derivatives reduced cell viability at concentrations about six times higher than those observed with MitoQ and SkQ1. A toxicity ranking for both cell lines was produced: MC<sub>4</sub> < MC<sub>7.2</sub> < MC<sub>3</sub> < MC<sub>6.2</sub>. These results suggest that C-6 carbon linker and the presence of a pyrogallol group result in lower cytotoxicity. MC<sub>3</sub> and MC<sub>6.2</sub> affected the mitochondrial function more significantly relative to MitoQ, SkQ1, resveratrol and CoQ<sub>10</sub>, while MC<sub>4</sub> and MC<sub>7.2</sub> displayed around 100–1000 times less cytotoxicity than SkQ1 and MitoQ. Based on the mitochondrial and cytotoxicity cellular data, MC<sub>4</sub> and MC<sub>7.2</sub> are proposed as leads that can be optimized to develop safe drug candidates with therapeutic application in mitochondrial oxidative stress-related diseases.Carlos FernandesAfonso J. C. VideiraCaroline D. VelosoSofia BenfeitoPedro SoaresJoão D. MartinsBeatriz GonçalvesJosé F. S. DuarteAntónio M. S. SantosPaulo J. OliveiraFernanda BorgesJosé TeixeiraFilomena S. G. SilvaMDPI AGarticlephenolic-based mitochondriotropic antioxidantsquinone-based mitochondriotropic antioxidantsnon-targeted antioxidantsMicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1605, p 1605 (2021) |
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phenolic-based mitochondriotropic antioxidants quinone-based mitochondriotropic antioxidants non-targeted antioxidants Microbiology QR1-502 |
| spellingShingle |
phenolic-based mitochondriotropic antioxidants quinone-based mitochondriotropic antioxidants non-targeted antioxidants Microbiology QR1-502 Carlos Fernandes Afonso J. C. Videira Caroline D. Veloso Sofia Benfeito Pedro Soares João D. Martins Beatriz Gonçalves José F. S. Duarte António M. S. Santos Paulo J. Oliveira Fernanda Borges José Teixeira Filomena S. G. Silva Cytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative Analysis |
| description |
Mitochondriotropic antioxidants (MC<sub>3</sub>, MC<sub>6.2</sub>, MC<sub>4</sub> and MC<sub>7.2</sub>) based on dietary antioxidants and analogs (caffeic, hydrocaffeic, trihydroxyphenylpropanoic and trihydroxycinnamic acids) were developed. In this study, we evaluate and compare the cytotoxicity profile of novel mitochondria-targeted molecules (generally known as MitoCINs) on human HepG2 and differentiated SH-SY5Y cells with the quinone-based mitochondria-targeted antioxidants MitoQ and SkQ<sub>1</sub> and with two non-targeted antioxidants, resveratrol and coenzyme Q<sub>10</sub> (CoQ<sub>10</sub>). We further evaluate their effects on mitochondrial membrane potential, cellular oxygen consumption and extracellular acidification rates. Overall, MitoCINs derivatives reduced cell viability at concentrations about six times higher than those observed with MitoQ and SkQ1. A toxicity ranking for both cell lines was produced: MC<sub>4</sub> < MC<sub>7.2</sub> < MC<sub>3</sub> < MC<sub>6.2</sub>. These results suggest that C-6 carbon linker and the presence of a pyrogallol group result in lower cytotoxicity. MC<sub>3</sub> and MC<sub>6.2</sub> affected the mitochondrial function more significantly relative to MitoQ, SkQ1, resveratrol and CoQ<sub>10</sub>, while MC<sub>4</sub> and MC<sub>7.2</sub> displayed around 100–1000 times less cytotoxicity than SkQ1 and MitoQ. Based on the mitochondrial and cytotoxicity cellular data, MC<sub>4</sub> and MC<sub>7.2</sub> are proposed as leads that can be optimized to develop safe drug candidates with therapeutic application in mitochondrial oxidative stress-related diseases. |
| format |
article |
| author |
Carlos Fernandes Afonso J. C. Videira Caroline D. Veloso Sofia Benfeito Pedro Soares João D. Martins Beatriz Gonçalves José F. S. Duarte António M. S. Santos Paulo J. Oliveira Fernanda Borges José Teixeira Filomena S. G. Silva |
| author_facet |
Carlos Fernandes Afonso J. C. Videira Caroline D. Veloso Sofia Benfeito Pedro Soares João D. Martins Beatriz Gonçalves José F. S. Duarte António M. S. Santos Paulo J. Oliveira Fernanda Borges José Teixeira Filomena S. G. Silva |
| author_sort |
Carlos Fernandes |
| title |
Cytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative Analysis |
| title_short |
Cytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative Analysis |
| title_full |
Cytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative Analysis |
| title_fullStr |
Cytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative Analysis |
| title_full_unstemmed |
Cytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative Analysis |
| title_sort |
cytotoxicity and mitochondrial effects of phenolic and quinone-based mitochondria-targeted and untargeted antioxidants on human neuronal and hepatic cell lines: a comparative analysis |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/a860ae5232fb4fd5a4306babf39f3851 |
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