Effect of ochratoxin A on rat liver mitochondrial respiration and oxidative phosphorylation

Wei, Yau‐Huei; Lu, C Y; Lin, Teng‐Nan; Wei, Ru‐Dong

doi:10.1016/0300-483x(85)90046-0

Cited by 62 publications

(38 citation statements)

References 25 publications

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“…The treatment of isolated renal proximal tubules with large concentrations of OTA resulted in an inhibition of mitochondrial respiration (Aleo et al 1991). Other in vitro studies applying direct treatments of mitochondrial preparations showed that OTA affected respiration and oxidative phosphorylation through an impairment of the mitochondrial membrane and an inhibition of the succinatesupported electron transfer activities of the respiratory chain (Wei et al 1985). In addition, ATP synthesis in mitochondria isolated from renal cortex was significantly inhibited by micromolar concentrations of OTA ( Jung and Endou 1989).…”

Section: Mitochondrial Dysfunctionsmentioning

confidence: 96%

Ochratoxin A: Potential epigenetic mechanisms of toxicity and carcinogenicity

Schilter

Marin-Kuan

Delatour

et al. 2005

Food Additives & Contaminants

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Assessment of the significance to human health of ochratoxin A (OTA) in food is limited by a lack of human toxicity data. Therefore, OTA risk evaluation relies mainly on the use of animal data, with renal carcinogenicity in rat being considered as the pivotal effect. The elucidation of the mechanism of action would improve the use of the carcinogenicity data for risk assessment. Direct genotoxicity versus epigenetic mechanisms appears to be a key question. In this presentation, new biochemical and toxicogenomic results obtained in a recent European project (EU-Grant # QLK1-CT-2001-011614) will be summarized in the context of previously reported mechanisms of action including inhibition of protein synthesis, production of oxidative stress and alteration of cell signalling. Amongst others, the new data indicate that chronic administration of a carcinogenic dose of OTA affected cell-signalling pathways resulting in a significantly reduced renal antioxidant defence and increased oxidative DNA damage. These data confirm previous hypotheses involving oxidative stress as a possible key epigenetic mechanism of OTA toxicity and carcinogenicity.

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Section: Mitochondrial Dysfunctionsmentioning

confidence: 96%

Ochratoxin A: Potential epigenetic mechanisms of toxicity and carcinogenicity

Schilter

Marin-Kuan

Delatour

et al. 2005

Food Additives & Contaminants

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“…These results suggest that the DIOS-induced effect on intracellular ATP concentrations is independent from or depends only slightly on the antioxidant property of the flavonoid. It is also important to note, that based on the previous studies the ATPdepleting effect of OTA is resulted from the inhibition of mitochondrial respiratory chain but its toxic effect is not related directly to the ATP synthase enzyme [27,[52][53][54]. On the other hand, DIOS abolished the negative effect of OTA on ATP system however, the inhibition of ATP synthase by olygomicin cannot be alleviated by DIOS.…”

Section: Diosmetin Versus Atp Depleting Effect Of Ochratoxin Amentioning

confidence: 89%

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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“…Induction of mitochondrial oxidative stress within OTA toxicity was detected by Wang et al, (2017) which was attributed to the oxidative effect of OTA on mitochondrial membrane ingredients with subsequent lipid peroxidation, decrease in mitochondrial membrane potential, leakage of cytochromec into the cytosol with reduction in ATP production (Chopra et al, 2010) with impairment of electron transport in mitochondrial respiratory chain (Wei et al, 1985). On the other side El Golli Bennour et al, (2009) detected the insignificant effect of oxidative stress in OTA induced toxicity, and in the same conclusion Bouaziz et al, (2011) suggested that ROS was created due to mitochondrial impairment rather than a mechanism of OTA induced toxicities.…”

Section: Plate (B)mentioning

confidence: 99%