Toxicokinetics and toxicodynamics of ochratoxin A, an update

Ringot, Diana; Chango, Abalo; Schneider, Yves‐Jacques; Larondelle, Yvan

doi:10.1016/j.cbi.2005.10.106

Cited by 418 publications

(340 citation statements)

References 183 publications

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“…1) is a fungal metabolite produced by several subspecies of the genera Penicillium and Aspergillus. Their widespread occurrence and the persistence of OTA in the food chain may contribute to a significant OTA exposure to humans [25,26]. In fact OTA has been frequently found in the human blood [20].…”

Section: Introductionmentioning

confidence: 99%

Ochratoxin A induces apoptosis in neuronal cells

et al. 2009

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The mycotoxin ochratoxin A (OTA), which is produced by Aspergillus and Penicillium subspecies, is a frequently present contaminant of food and feedstuffs. OTA exhibits a wide range of toxic activities including nephro-and hepatotoxicity. However, little is known regarding potential neurotoxic effects of OTA. In the present study primary neurons as well as SH-SY5Y neuronal cells were incubated with increasing concentrations of OTA (0.1-2.5 lmol/L). OTA treatment resulted in a dose-dependent increase in cytotoxicity in both neuronal cell types. Caspase-9 and caspase-3 were activated in response to OTA treatment. Furthermore, caspase inhibitors were effective in partly counteracting OTA induced neurocytotoxicity. OTA induced apoptosis was accompanied by a loss of mitochondria membrane potential. Overall, present data indicated that OTA is neurotoxic at relatively low concentrations. OTA induced neurotoxicity seems to be, at least party, mediated by apoptosis. OTA may contribute to the pathogenesis of neurodegenerative diseases (e.g. Alzheimer's and Parkinson's disease) in which apoptotic processes are centrally involved.

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Section: Introductionmentioning

confidence: 99%

Ochratoxin A induces apoptosis in neuronal cells

et al. 2009

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“…The ATP depleting effect of OTA is not clearly understood yet but previous studies suggest its influence on the mitochondrial respiratory chain caused by the inhibition of mitochondrial phosphate transport and/or the direct effect on the electron transport chain (inhibition of succinate-supported electron activities) [27]. Based on our preliminary measurements on MDCK cells, low OTA concentrations (5-15 lM) cause major changes on ATP levels at least after 24-h treatment (data not shown).…”

Section: Diosmetin Versus Atp Depleting Effect Of Ochratoxin Amentioning

confidence: 73%

“…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%

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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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“…OTA was reported to have inhibitor effect on mitochondrial respiration which may be accounted for the impairment of renal function due to the depletion of ATP (Duarte et al, 2009). Although several mechanisms were suggested for the mode of action of OTA but the strong ATP depleting effect seems to be the most pronounced (Ringot et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Papaya fruits extracts enhance the antioxidant capacity and modulate the genotoxicity and oxidative stress in the kidney of rats fed ochratoxin A-contaminated diet

2017

J App Pharm Sci

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Ochratoxin A (OTA) is a mycotoxin widespread contaminates food and has potent nephrotoxicity. The present study aimed to determine total phenolics and DPPH radical scavenging activity for water and ethanolic extracts (WE and EE) of papaya fruits and evaluation of the protective role of these extracts against OTA-induced oxidative damage and nephrotoxicity in rats. Sixty male Sprague-Dawley rats were divided into six groups and treated for 21 days as follow: the control group, OTA-treated group (3 mg/kg diet), WE or EE extracts treated groups (250 mg/kg b.w) and OTA plus WE or EE-treated groups. Blood and kidney samples were collected for different biochemical, cytogenetical and histological analyses. The results showed that WE and EE contained 408.54 and 296.85 g/kg total phenolic, respectively and DPPH radical scavenging activity was higher in WE than EE. Animals fed OTA-contaminated diet showed signs of toxicity as indicated by the significant decrease in body weight gain and food intake, the disturbances in kidney biochemical indices, increase DNA fragmentation and oxidative stress markers, the decrease in antioxidant enzymes activities and gene expression as well as severe histological and histochemical changes in the kidney tissues. Both extracts succeeded to counteract these alterations and WE was more effective than EE. These results concluded that papaya fruits extracts succeeded to a great extant to counteract the oxidative stress of OTA and to protect the kidney against its toxic effects and may be promising candidate as food supplement for the protection against OTA in high endemic area.

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Toxicokinetics and toxicodynamics of ochratoxin A, an update

Cited by 418 publications

References 183 publications

Ochratoxin A induces apoptosis in neuronal cells

Ochratoxin A induces apoptosis in neuronal cells

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

Papaya fruits extracts enhance the antioxidant capacity and modulate the genotoxicity and oxidative stress in the kidney of rats fed ochratoxin A-contaminated diet

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