Disturbed Hsp70 and Hsp27 expression and thiol redox status in porcine kidney PK15 cells provoked by individual and combined ochratoxin A and citrinin treatments

•OTA and CTN exert cytotoxic synergism in porcine kidney PK15 cells.•Single and combined toxins decreased total thiols and GSH/GSSG ratio.•Hsp70 and Hsp27 were differentially affected by single and dual mycotoxin treatment.•OTA and CTN synergistically affect Hsps and redox homeostasis. The aim of th...

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Veröffentlicht in:Food and chemical toxicology 2014-09, Vol.71, p.97-105
Hauptverfasser: Šegvić Klarić, Maja, Medić, Nevena, Hulina, Andrea, Žanić Grubišić, Tihana, Rumora, Lada
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Sprache:eng
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Zusammenfassung:•OTA and CTN exert cytotoxic synergism in porcine kidney PK15 cells.•Single and combined toxins decreased total thiols and GSH/GSSG ratio.•Hsp70 and Hsp27 were differentially affected by single and dual mycotoxin treatment.•OTA and CTN synergistically affect Hsps and redox homeostasis. The aim of this study was to explore the oxidative properties of ochratoxin A (OTA) and citrinin (CTN) as a possible underlying mechanism of their individual and/or combined cytotoxicity. Metabolic activity of PK15 porcine kidney cells was significantly reduced with OTA and CTN co-exposures, with synergistic cytotoxic interactions. Single CTN increased both reduced (GSH) and oxidized (GSSG) glutathione after 24h. However, GSH was significantly lowered with all OTA and CTN combined applications in synergistic manner after 12 and 24h. GSH/GSSG ratio was reduced in most single and dual treatments, which suggested the presence of oxidative stress. In addition, OTA and CTN exposures significantly decreased concentrations of total thiols, with mycotoxins interactions being synergistic or antagonistic. The expression levels of Hsps were differentially affected by single and dual mycotoxin(s) applications. Single OTA provoked significant down-regulation of Hsp70 and Hsp27 expressions, while CTN stimulated Hsps expressions. Hsps were also up-regulated by dual treatments, and this induction was much stronger then with single CTN. In conclusion, significant alterations in cellular redox status (glutathione, thiols) and protective mechanisms (Hsps) suggest that those disturbances might be involved in OTA and CTN individual and combined mechanisms of cytotoxicity.
ISSN:0278-6915
1873-6351
DOI:10.1016/j.fct.2014.06.002