Different apoptotic pathways induced by zearalenone, T-2 toxin and ochratoxin A in human hepatoma cells

Bouaziz, Chayma; Dein, Ossama Sharaf El; Golli, Emna El; Abid‐Essefi, Salwa; Brenner, Catherine; Lemaire, Christophe; Bacha, Hassen

doi:10.1016/j.tox.2008.08.020

Cited by 162 publications

(121 citation statements)

References 45 publications

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“…These findings are in line with current results [8] which emphasize a central role of the mitochondria in OTA induced caspase dependent apoptosis in liver cells.…”

Section: Discussionsupporting

confidence: 93%

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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“…These findings are in line with current results [8] which emphasize a central role of the mitochondria in OTA induced caspase dependent apoptosis in liver cells.…”

Section: Discussionsupporting

confidence: 93%

Ochratoxin A induces apoptosis in neuronal cells

et al. 2009

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“…4) and GSH/OTA (Plate D, Fig., 3) treated groups in descending order, that reflect the ability of Glutathione to keep DNA stability (at protective level) in concentration-dependent manner and even its ability to repair genome damage. Similar result was reported by Bouaziz et al, (2008) and El Golli Bennour et al, (2009). Erster et al, (2004 refer to dual effect of p53; first one represent a fast response of sensitive organs (thymus and spleen) to oxidative stress through induction of mitochondria-mediated caspase-3 activation (that could explain the un-associated release of caspase-3 independent of cytochrome-c, in the present study), the other one is delayed response (less sensitive organs; liver and kidneys); in which P53 act as a transcriptional factors for apoptogenic proteins.…”

Section: Plate (B)supporting

confidence: 91%

Prevalence of Ochratoxigenic Fungi and Ochratoxin A Residues in Animal Feeds and Modulation of Their Toxic Effects by Glutathione

Atef¹,

Shafei²,

Mansour³

et al. 2018

Int.J.Curr.Microbiol.App.Sci

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“…ZEN can be bound to the estrogen receptors (4,5) resulting in a hyperestrogenicity syndrome in several animal species, especially pigs (6) . In addition, ZEN has been shown to be immunotoxic (7) , hepatonephrotoxic (8) and enhancer of lipid peroxidation (9) . Using in vitro approaches, we have investigated the effect of ZEN and its metabolites: alpha zearalenol (a-ZOL) and beta zearalenol (b-ZOL) on a pig epithelial cell line: IPEC-1, in term of cell viability, trans-epithelial electric resistance (TER) and synthesis of some inflammatory cytokines: IL-1 beta; TNF alpha and IL-8.…”

mentioning

confidence: 99%

Effects of zearalenone and its metabolites on the swine epithelial intestinal cell line: IPEC 1

2013

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Zearalenone (ZEN) is a mycotoxin that can be produced by several Fusarium fungi (1,2) and it exists widely in maize, barley, wheat, oats, sorghum and sesame seeds, as well as in hay and corn silage, which are ingredients in many food products for humans or animals (3) . ZEN can be bound to the estrogen receptors (4,5) resulting in a hyperestrogenicity syndrome in several animal species, especially pigs (6) . In addition, ZEN has been shown to be immunotoxic (7) , hepatonephrotoxic (8) and enhancer of lipid peroxidation (9) . Using in vitro approaches, we have investigated the effect of ZEN and its metabolites: alpha zearalenol (a-ZOL) and beta zearalenol (b-ZOL) on a pig epithelial cell line: IPEC-1, in term of cell viability, trans-epithelial electric resistance (TER) and synthesis of some inflammatory cytokines: IL-1 beta; TNF alpha and IL-8. For the viability assays, IPEC-1 cells were cultivated in 96 wells plates and treated or not with 0.1-100 M ZEN and metabolites. The TER and cytokine synthesis assays were performed using cells cultivated in transwell inserts and treated for 9 days with ZEN and metabolites (25 and 50 M). Using an XTT and a neutral red assay we have shown that both ZEN and ZEN metabolites induced a dose dependent decrease of cell viability, with beta-ZOL being the most toxic.The trans-epithelial electric resistance measurement, showed that 25 M of beta ZOL induced a light increase of TER values but no effect was observed for ZEN or alpha ZOL. At 50 M, alpha and beta ZOL induced a time decrease of TER values, all along the experiment; thus at day 9, the TER value in the treated inserts were 17.8 % for alpha ZOL and 21.6 % for beta ZOL from the unintoxicated control. By contrast, ZEN induced only a slight decrease of the TER values, that was retrieved at day 9 (95.6% in ZEN treated insert compared with 100% in the control).The analyse of the cytokine concentration in the supernatant from the apical (AC) and baso-lateral (BC) compartments of the inserts showed that the IPEC-1 cells were not able to synthesize IL-1 beta or TNF alpha. By contrast, IPEC-1 cells were able to synthesize IL-8; the synthesis was similar among the treatments in the BC, but an induction of the IL-8 synthesis by the toxins was observed in the AC. Taken together, our results showed that ZEN and its metabolites could interfere with the barrier function of the intestine and with the capacity of the intestinal cells to realise an inflammatory response.

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Different apoptotic pathways induced by zearalenone, T-2 toxin and ochratoxin A in human hepatoma cells

Cited by 162 publications

References 45 publications

Ochratoxin A induces apoptosis in neuronal cells

Ochratoxin A induces apoptosis in neuronal cells

Prevalence of Ochratoxigenic Fungi and Ochratoxin A Residues in Animal Feeds and Modulation of Their Toxic Effects by Glutathione

Effects of zearalenone and its metabolites on the swine epithelial intestinal cell line: IPEC 1

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