Insights into the intracellular mechanisms of citronellal in Candida albicans: implications for reactive oxygen species-mediated necrosis, mitochondrial dysfunction, and DNA damage
Abstract INTRODUCTION Citronellal (Cit) possesses antifungal activity and has possible implications for reactive oxygen species (ROS) generation in Candida albicans. In this study, the effects of Cit on ROS generation and the mechanisms by which Cit exerts anti-Candida effects were examined. METHODS...
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ftdoajarticles:oai:doaj.org/article:5d9529a9680f4225a13c48578b5a59dd 2023-05-15T15:13:12+02:00 Insights into the intracellular mechanisms of citronellal in Candida albicans: implications for reactive oxygen species-mediated necrosis, mitochondrial dysfunction, and DNA damage Venkata Saibabu Shweta Singh Moiz A. Ansari Zeeshan Fatima Saif Hameed https://doi.org/10.1590/0037-8682-0114-2017 https://doaj.org/article/5d9529a9680f4225a13c48578b5a59dd EN eng Sociedade Brasileira de Medicina Tropical (SBMT) http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822017000400524&lng=en&tlng=en https://doaj.org/toc/1678-9849 1678-9849 doi:10.1590/0037-8682-0114-2017 https://doaj.org/article/5d9529a9680f4225a13c48578b5a59dd Revista da Sociedade Brasileira de Medicina Tropical, Vol 50, Iss 4, Pp 524-529 Reactive oxygen species Necrosis Mitochondria DNA Propidium iodide Candida albicans Arctic medicine. Tropical medicine RC955-962 article ftdoajarticles https://doi.org/10.1590/0037-8682-0114-2017 2022-12-30T23:10:45Z Abstract INTRODUCTION Citronellal (Cit) possesses antifungal activity and has possible implications for reactive oxygen species (ROS) generation in Candida albicans. In this study, the effects of Cit on ROS generation and the mechanisms by which Cit exerts anti-Candida effects were examined. METHODS A 2′,7′-dichlorodihydrofluorescein diacetate assay was used to assess oxidative damage. Cell necrosis was determined by flow cytometry after FITC-Annexin V staining. Mitochondrial function was studied based on mitochondrial potential, metabolic activity (MTT assay), and phenotypic susceptibility on a non-fermentable carbon source. Membrane intactness and DNA damage were estimated by a propidium iodide (PI) uptake assay and 4',6-diamidino-2-phenylindole (DAPI) staining. RESULTS ROS generation was enhanced in response to Cit, leading to necrosis (2%). Additional hallmarks of cell death in response to Cit, such as mitochondrial membrane depolarization and DNA damage, were also observed. Cit treatment resulted in dysfunctional mitochondria, as evidenced by poor labeling with the mitochondrial membrane potential-sensitive probe rhodamine B, reduced metabolic activity (61.5%), and inhibited growth on a non-fermentable carbon source. Furthermore, Cit induced DNA damage based on DAPI staining. These phenotypes were reinforced by RT-PCR showing differences in gene expression (30-60%) between control and Cit-treated cells. Finally, PI uptake in the presence of sodium azide confirmed non-intact membranes and suggested that Cit activity is independent of the energy status of the cell. CONCLUSIONS Cit possesses dual anticandidal mechanisms, including membrane-disruptive and oxidative damage. Taken together, our data demonstrated that cit could be used as a prominent antifungal drug. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Revista da Sociedade Brasileira de Medicina Tropical 50 4 524 529 |
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Reactive oxygen species Necrosis Mitochondria DNA Propidium iodide Candida albicans Arctic medicine. Tropical medicine RC955-962 |
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Reactive oxygen species Necrosis Mitochondria DNA Propidium iodide Candida albicans Arctic medicine. Tropical medicine RC955-962 Venkata Saibabu Shweta Singh Moiz A. Ansari Zeeshan Fatima Saif Hameed Insights into the intracellular mechanisms of citronellal in Candida albicans: implications for reactive oxygen species-mediated necrosis, mitochondrial dysfunction, and DNA damage |
topic_facet |
Reactive oxygen species Necrosis Mitochondria DNA Propidium iodide Candida albicans Arctic medicine. Tropical medicine RC955-962 |
description |
Abstract INTRODUCTION Citronellal (Cit) possesses antifungal activity and has possible implications for reactive oxygen species (ROS) generation in Candida albicans. In this study, the effects of Cit on ROS generation and the mechanisms by which Cit exerts anti-Candida effects were examined. METHODS A 2′,7′-dichlorodihydrofluorescein diacetate assay was used to assess oxidative damage. Cell necrosis was determined by flow cytometry after FITC-Annexin V staining. Mitochondrial function was studied based on mitochondrial potential, metabolic activity (MTT assay), and phenotypic susceptibility on a non-fermentable carbon source. Membrane intactness and DNA damage were estimated by a propidium iodide (PI) uptake assay and 4',6-diamidino-2-phenylindole (DAPI) staining. RESULTS ROS generation was enhanced in response to Cit, leading to necrosis (2%). Additional hallmarks of cell death in response to Cit, such as mitochondrial membrane depolarization and DNA damage, were also observed. Cit treatment resulted in dysfunctional mitochondria, as evidenced by poor labeling with the mitochondrial membrane potential-sensitive probe rhodamine B, reduced metabolic activity (61.5%), and inhibited growth on a non-fermentable carbon source. Furthermore, Cit induced DNA damage based on DAPI staining. These phenotypes were reinforced by RT-PCR showing differences in gene expression (30-60%) between control and Cit-treated cells. Finally, PI uptake in the presence of sodium azide confirmed non-intact membranes and suggested that Cit activity is independent of the energy status of the cell. CONCLUSIONS Cit possesses dual anticandidal mechanisms, including membrane-disruptive and oxidative damage. Taken together, our data demonstrated that cit could be used as a prominent antifungal drug. |
format |
Article in Journal/Newspaper |
author |
Venkata Saibabu Shweta Singh Moiz A. Ansari Zeeshan Fatima Saif Hameed |
author_facet |
Venkata Saibabu Shweta Singh Moiz A. Ansari Zeeshan Fatima Saif Hameed |
author_sort |
Venkata Saibabu |
title |
Insights into the intracellular mechanisms of citronellal in Candida albicans: implications for reactive oxygen species-mediated necrosis, mitochondrial dysfunction, and DNA damage |
title_short |
Insights into the intracellular mechanisms of citronellal in Candida albicans: implications for reactive oxygen species-mediated necrosis, mitochondrial dysfunction, and DNA damage |
title_full |
Insights into the intracellular mechanisms of citronellal in Candida albicans: implications for reactive oxygen species-mediated necrosis, mitochondrial dysfunction, and DNA damage |
title_fullStr |
Insights into the intracellular mechanisms of citronellal in Candida albicans: implications for reactive oxygen species-mediated necrosis, mitochondrial dysfunction, and DNA damage |
title_full_unstemmed |
Insights into the intracellular mechanisms of citronellal in Candida albicans: implications for reactive oxygen species-mediated necrosis, mitochondrial dysfunction, and DNA damage |
title_sort |
insights into the intracellular mechanisms of citronellal in candida albicans: implications for reactive oxygen species-mediated necrosis, mitochondrial dysfunction, and dna damage |
publisher |
Sociedade Brasileira de Medicina Tropical (SBMT) |
url |
https://doi.org/10.1590/0037-8682-0114-2017 https://doaj.org/article/5d9529a9680f4225a13c48578b5a59dd |
geographic |
Arctic |
geographic_facet |
Arctic |
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Arctic |
genre_facet |
Arctic |
op_source |
Revista da Sociedade Brasileira de Medicina Tropical, Vol 50, Iss 4, Pp 524-529 |
op_relation |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822017000400524&lng=en&tlng=en https://doaj.org/toc/1678-9849 1678-9849 doi:10.1590/0037-8682-0114-2017 https://doaj.org/article/5d9529a9680f4225a13c48578b5a59dd |
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https://doi.org/10.1590/0037-8682-0114-2017 |
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Revista da Sociedade Brasileira de Medicina Tropical |
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50 |
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524 |
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