The interaction of flavonoids with mitochondria: effects on energetic processes

Dorta, Daniel Junqueira; Pigoso, Acácio A.; Mingatto, Fábio Ermínio; Rodrigues, Tiago; Prado, I M R; Helena, Anaísa F.C.; Uyemura, Sérgio Akira; Santos, Antônio Carlos dos; Curti, Carlos

doi:10.1016/j.cbi.2005.02.004

Cited by 147 publications

(100 citation statements)

References 41 publications

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“…Chrysin resulted in lower (16%) while fisetin caused higher (46%) decrease of ATP than the above listed flavonoid aglycones. These results are in accordance with the previous investigations discussed in the introductory section [5][6][7][8][9]. Interestingly, after 24-h treatment a significant elevation (about 20%) of ATP levels was caused by luteolin.…”

Section: Effects Of Flavonoid Aglycones On Atp Levels Of Mdck Cellssupporting

confidence: 93%

“…1) to explore their influence on intracellular ATP levels in MDCK kidney-derived cell line using primarily the luciferin-luciferase ATP dependent bioluminescent reaction. In agreement with the previous studies most of the applied flavonoids caused no or only a mild decrease of intracellular ATP concentrations [5][6][7][8][9]. In contrast, the flavone DIOS exerted a significant increase in ATP levels therefore, our experiments were focused on the investigation of this aglycone.…”

Section: Introductionsupporting

confidence: 90%

“…Previous studies highlighted that besides their scavenger property flavonoids exerted influence on the activity of several enzymes, transporters and on cell signaling pathways [1]. Interestingly, based on our current knowledge all of the previous investigations suggested that at least some of the studied flavonoids were able to decrease intracellular ATP levels [5][6][7][8][9]. Chinnam et al described the inhibition of Escherichia coli (E. coli) ATP synthase on purified F 1 subunit or membrane bound F 1 Fo complexes related to different dietary bioflavonoids [5].…”

Section: Introductionmentioning

confidence: 84%

“…In another study, Kanno et al found naringenin-induced significant decrease of intracellular ATP levels and increased dose-dependent hyperpolarization of mitochondrial membrane potential in HL-60 cells [7]. Moreover, Mathiesen et al and Dorta et al reported uncoupled oxidative phosphorylation due to C-methylated flavonoids [8] and substantial respiratory chain inhibition by quercetin and galangin [9] in rat liver mitochondria. In our literature survey we have not found any references observing that certain flavonoids might increase intracellular ATP levels.…”

Section: Introductionmentioning

confidence: 96%

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Flavonoid diosmetin increases ATP levels in kidney cells and relieves ATP depleting effect of ochratoxin A

Poór

Veres

Jakus

et al. 2014

Journal of Photochemistry and Photobiology B: Biology

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a b s t r a c tDiosmetin (DIOS) is a flavone aglycone commonly occurring in citrus species and olive leaves, in addition it is one of the active ingredients of some medications. Based on both in vitro and in vivo studies several beneficial effects are attributed to DIOS but the biochemical background of its action seems to be complex and it has not been completely explored yet. Previous investigations suggest that most of the flavonoid aglycones have negative effect on ATP synthesis in a dose dependent manner. In our study 17 flavonoids were tested and interestingly DIOS caused a significant elevation of intracellular ATP levels after 6-and 12-h incubation in MDCK kidney cells. In order to understand the mechanism of action, intracellular ATP and protein levels, ATP/ADP ratio, cell viability and ROS levels were determined after DIOS treatment. In addition, impacts of different enzyme inhibitors and effect of DIOS on isolated rat liver mitochondria were also tested. Finally, the influence of DIOS on the ATP depleting effect of the mycotoxin, ochratoxin A was also investigated. Our major conclusions are the followings: DIOS increases intracellular ATP levels both in kidney and in liver cells. Inhibition of glycolysis or citric acid cycle does not decrease the observed effect. DIOS-induced elevation of ATP levels is completely abolished by the inhibition of ATP synthase. DIOS is able to completely reverse the ATP-depleting effect of the mycotoxin, ochratoxin A. Most probably the DIOS-induced impact on ATP system does not originate from the antioxidant property of DIOS. Based on our findings DIOS may be promising agent to positively influence ATP depletion caused by some metabolic poisons.

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Section: Effects Of Flavonoid Aglycones On Atp Levels Of Mdck Cellssupporting

confidence: 93%

Section: Introductionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 96%

See 2 more Smart Citations

Flavonoid diosmetin increases ATP levels in kidney cells and relieves ATP depleting effect of ochratoxin A

Poór

Veres

Jakus

et al. 2014

Journal of Photochemistry and Photobiology B: Biology

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“…For that reason, novel highthroughput methods employ mitochondria as a bio marker for drug safety in pharmaceutical industry drug research (Dykens & Will, 2007). Furthermore, previous studies report the inhibitory effect of flavonoids on mitochondrial respiration (Dorta et al, 2005;Elingold et al, 2008).The respiratory chain inhibition promoted by several flavonoids has been frequently associated with the oxidation potentials of these compounds, which are commonly located in similar range as the mitochondrial redox centers (Firuzi, Lacanna, Petrucci, Marrosu, & Saso, 2005;Hodnick, Mllosavljevic, Nelson, & Pardini, 1988).…”

Section: Discussionmentioning

confidence: 99%

Antioxidant capacity and toxicological evaluation ofPterospartum tridentatumflower extracts

Ferreira

Dinis

Azedo

et al. 2012

CyTA - Journal of Food

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Pterospartum tridentatum Willk. (prickled broom) is an autochthonous plant, common in Portuguese territory. The yellow flowers are used in traditional medicine, as a potential cure for all body illnesses, mainly to treat throat irritations or for diabetes, hypertension and hypercholesterolemia therapy. Despite its traditional use, no toxicological assessment has been performed to our knowledge. A high antioxidant activity of P. tridentatum flower water extract was found, in good agreement with its electrospray ionisation-mass spectroscopy (ESI-MS) spectrum which revealed the presence of several flavonoids, such as luteolin-O-(O-acetyl)-glucuronide, luteolin-Oglucuronide or isorhamnetin-O-hexoside. Mitocondrial respiratory rates (state 4, state 3 and FCCP-stimulated respiration) and respiratory indexes (respiratory control and P/O ratios) showed no consistent decrease of respiratory and phosphorylative efficiencies for the concentrations tested (up to 500 mg.mL 71 ). Cytotoxicity evaluation, using MTT assay, was in agreement with the previous results. In conclusion, for the concentration range commonly used, P. tridentatum flower usage can be regarded as harmless and credible.Keywords: antioxidant capacity; cytotoxicity; oxidative phosphorylation; phytotherapy; Pterospartum tridentatum (L.); Willk.; toxicologic evaluation Pterospartum tridentatum Willk. es una planta auto´ctona comu´n en el territorio portugue´s. Las flores amarillas se usan en medicina tradicional como cura potencial para todas las enfermedades, especialmente para tratamientos de irritacio´n de garganta o para tratamientos contra diabetes, hipertensio´n o hipercolesterolemia. A pesar de su uso tradicional, ninguna evaluacio´n toxicolo´gica se ha llevado a cabo. Se encontro´una alta actividad antioxidante de extracto acuoso de flor de P. Tridentatum, concordando con su espectro ESI-MS, el cual revelo´la presencia de varios flavonoides, como luteolina O-(O-acetil)-glucuro´nido, luteolina-Oglucuro´nido o isorramntina-O-hexo´sido. Las frecuencias respiratorias mitocondriales (estado 4, estado 3 y respiracio´n estimulada por FCCP) mostraron un descenso no consistente de eficiencia respiratoria y fosforilativa para las concentraciones analizadas (hasta 500 mg.mL -1 ). La evaluacio´n de citotoxicidad, usando ensayo MTT, coincidio´con los resultados previos. En conclusio´n, para las concentraciones comu´nmente empleadas, el uso de las flores de P. tridentatum se puede considerar inocuo y verosı´mil.Palabras claves: capacidad antioxidante; citotoxicidad; fosforilacio´n oxidativa; fitoterapia; Pterospartum tridentatum (L.) Willk; evaluacio´n toxicolo´gica Abbreviations: ESI, electrospray ionization; FCCP, carbonyl cyanide p-trifluoromethoxyphenylhydrazone; HepG2, a human hepatoma cell line; MS, mass spectrometry; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; P/O ratio, ratio of ADP molecules phosphorylated to atoms of oxygen consumed; RCR, respiratory control ratio (state 3 respiratory rate/state 4 respiratory rate)

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Effect of quercetin on oxidative nuclear and mitochondrial DNA damage

et al. 2008

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Quercetin is a well-investigated antioxidant known to protect cells against oxidative nuclear DNA damage. There is no knowledge regarding its effect on oxidative mitochondrial DNA damage. In this study we investigated the effect of quercetin on oxidatively-injured DNA. Cell-free and cell studies were performed. Cell-free analyses carried out on plasmidic DNA showed that quercetin protects from all oxidative challenges used. Cellular studies were carried out on NCTC 2544 cells which were insulted with hydrogen peroxide and UVC radiations. Nuclear and mitochondrial DNAs were analysed by measuring DNA damage with a quantitative polymerase chain reaction. Quercetin supplementation showed significant genoprotective activity on mitochondrial DNA when hydroperoxide was used. The evidence of the protection afforded by quercetin suggests that this flavonoid may play an important role on mitochondrial genome stability.

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The interaction of flavonoids with mitochondria: effects on energetic processes

Cited by 147 publications

References 41 publications

Flavonoid diosmetin increases ATP levels in kidney cells and relieves ATP depleting effect of ochratoxin A

Flavonoid diosmetin increases ATP levels in kidney cells and relieves ATP depleting effect of ochratoxin A

Antioxidant capacity and toxicological evaluation ofPterospartum tridentatumflower extracts

Effect of quercetin on oxidative nuclear and mitochondrial DNA damage

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