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Characterization of lapachol cytotoxicity: contribution of glutathione depletion for oxidative stress in Saccharomyces cerevisiae.

Abstract：

:Over the years, quinones or its derivatives have been extensively studied due to their broad therapeutic spectrum. However, due to the significant structural differences between the individual naturally occurring quinones, investigation of the precise mechanism of their action is essential. In this context, we have analyzed the mechanism of lapachol [4-hydroxy-3-(3-methylbut-2-enyl)naphthalene-1,2-dione] toxicity using Saccharomyces cerevisiae as eukaryotic model organism. Analyzing yeast (wild type, sod1∆, and gsh1∆) cell growth, we observed a strong cytostatic effect caused by lapachol exposure. Moreover, survival of cells was affected by time- and dose-dependent manner. Interestingly, sod1∆ cells were more prone to lapachol toxicity. In this sense, mitochondrial functioning of sod1∆ cells were highly affected by exposure to this quinone. Lapachol also decreased glutathione (GSH) levels in wild type and sod1∆ cells even though glutathione disulfide (GSSG) remained unchanged. We believe that reduction of GSH contents has contributed to the enhancement of lipid peroxidation and intracellular oxidation, effect much more pronounced in sod1∆ cells. Overall, the collected data suggest that although lapachol can act as an oxidant, it seems that the main mechanism of its action initially consists in alkylation of intracellular targets such as GSH and then generating oxidative stress.

journal_name

Folia Microbiol (Praha)

journal_title

Folia microbiologica

authors

Castro FAV,de Souza GFM,Pereira MD

doi

10.1007/s12223-019-00722-2

subject

Has Abstract

pub_date

2020-02-01 00:00:00

pages

197-204

issue

1

eissn

0015-5632

issn

1874-9356

pii

10.1007/s12223-019-00722-2

journal_volume

65

pub_type

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