title: Comparative mechanisms of zearalenone and ochratoxin A toxicities on cultured HepG2 cells: is oxidative stress a common process?
abstract: Zearalenone (ZEN) and Ochratoxin A (OTA) are structurally diverse fungal metabolites that can contaminate feed and foodstuff and can cause serious health problems for animals as well as for humans. In this study, we get further insight of the molecular aspects of ZEN and OTA toxicities in cultured human HepG2 hepatocytes. In this context, we have monitored the effects of ZEN and OTA on (i) cell viability, (ii) heat shock protein (Hsp) 70 and Hsp 27 gene expressions as a parameter of protective and adaptive response, (iii) oxidative damage, and (iv) cell death pathways. Our results clearly showed that both ZEN and OTA inhibit cell proliferation. For ZEN, a significant induction of Hsp 70 and Hsp 27 was observed. In the same conditions, ZEN generated an important amount of reactive oxygen species (ROS). Antioxidant supplements restored the major part of cell mortality induced by ZEN. However, OTA treatment downregulated Hsp 70 and Hsp 27 protein and mRNA levels and did not induce ROS generation. Antioxidant supplements did not have a significant effect on OTA-induced cell mortality. Using another cell system (Vero monkey kidney cells), we demonstrated that OTA downregulates three members of HSP 70 family: Hsp 70, Hsp 75, and Hsp 78. Our findings showed that oxidative damage seemed to be the predominant toxic effect for ZEN, while OTA toxicity seemed to be rather because of the absence of Hsps protective response. Furthermore, the two mycotoxins induced an apoptotic cell death.
authors.affiliation: Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Rue Avicenne, Monastir 5000, Tunisia.
authors.forename: Emna
authors.initials: E
authors.lastname: El Golli Bennour
authors.forename: Chayma
authors.initials: C
authors.lastname: Bouaziz
authors.forename: Moncef
authors.initials: M
authors.lastname: Ladjimi
authors.forename: Flore
authors.initials: F
authors.lastname: Renaud
authors.forename: Hassen
authors.initials: H
authors.lastname: Bacha
mesh_terms: D001393:Azoles / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D054833:Isoindoles; D009183:Mycotoxins / Q000737:chemistry / Q000633:toxicity*; D009793:Ochratoxins / Q000737:chemistry / Q000633:toxicity*; D016566:Organoselenium Compounds / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D018675:Toxicity Tests; D014810:Vitamin E / Q000494:pharmacology; D015025:Zearalenone / Q000737:chemistry / Q000633:toxicity*
chemical_list: D001393:Azoles; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D054833:Isoindoles; D009183:Mycotoxins; D009793:Ochratoxins; D016566:Organoselenium Compounds; D012333:RNA, Messenger; D014810:Vitamin E; C025589:ochratoxin A; C042986:ebselen; D015025:Zearalenone