Cytotoxicity and apoptosis induced by fumonisin B(1), beauvericin and ochratoxin A in porcine kidney PK15 cells: effects of individual and combined treatment.
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.
Klarić
Maja Segvić
MS
Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia. msegvic@pharma.hr
Rumora
Lada
L
Ljubanović
Danica
D
Pepeljnjak
Stjepan
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D047630:Depsipeptides / Q000633:toxicity*; D004357:Drug Synergism; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D037341:Fumonisins / Q000633:toxicity*; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D009793:Ochratoxins / Q000633:toxicity*; D013552:Swine
D047630:Depsipeptides; D037341:Fumonisins; D009793:Ochratoxins; C025589:ochratoxin A; C004456:beauvericin; C056933:fumonisin B1; D053148:Caspase 3