Cytotoxicity and apoptosis induced by fumonisin B(1), beauvericin and ochratoxin A in porcine kidney PK15 cells: effects of individual and combined treatment

Arch Toxicol. 2008 Apr;82(4):247-55. doi: 10.1007/s00204-007-0245-y. Epub 2007 Sep 19.

Abstract

The objective of this study was to determine individual and combined effects of fumonisin B(1) (FB(1)), beauvericin (BEA) and ochratoxin A (OTA) on porcine kidney epithelial PK15 cell survival by measuring lactate dehydrogenase (LDH) activity, apoptotic index and caspase-3 activity. Cells were treated with 0.05, 0.5 and 5 microg/ml of each mycotoxin or with the combinations of two or all three mycotoxins for 24 and 48 h. Changes in LDH and caspase-3 activity, and in apoptotic index showed that the cytotoxic and apoptotic effects of these mycotoxins were concentration- and time- dependent. Significant increase of LDH activity was observed after 48 h of exposure to the highest concentration of FB(1) (45%), BEA (84%) and OTA (77%), as compared to control. OTA increased caspase-3 activity after 24 h of treatment with 0.5 mug/mL (84%), while BEA (319%) and FB(1) (419%) significantly affected this enzyme activity after 48 h (P < 0.05). Increase of caspase-3 activity preceded significant morphological apoptotic changes, which were detected after 48 h of exposure to a single toxin. Combined treatment with FB(1), BEA and OTA resulted mostly in additive effects on LDH activity, and additive and synergistic effects on caspase-3 activity and apoptotic index.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Depsipeptides / toxicity*
  • Drug Synergism
  • Epithelial Cells / drug effects*
  • Epithelial Cells / pathology
  • Fumonisins / toxicity*
  • Kidney / cytology
  • Kidney / drug effects*
  • Kidney / pathology
  • Ochratoxins / toxicity*
  • Swine

Substances

  • Depsipeptides
  • Fumonisins
  • Ochratoxins
  • ochratoxin A
  • beauvericin
  • fumonisin B1
  • Caspase 3