Ochratoxin A induces nephrotoxicity and immunotoxicity through different MAPK signaling pathways in PK15 cells and porcine primary splenocytes.

Ochratoxin A (OTA) is reported to be a potent nephrotoxin and immunotoxin in animals and humans. However, the mechanisms underlying OTA toxicity have not been clearly determined until now. Toxicity of OTA and its mechanism was investigated in PK15 cells and in porcine primary splenocytes. The results showed that OTA at 2.0-8.0 μg/mL for 24 h induced cytotoxicity and apoptosis in a dose-dependent manner in PK 15 cells. OTA at 0.5-4.0 μg/mL for 24 h induced cytotoxicity and apoptosis in a dose-dependent manner in porcine primary splenocytes. In addition, OTA induced p38 and ERK1/2 phosphorylation both in PK15 cells and porcine primary splenocytes. Knock-down of p38 instead of ERK by their specific siRNA significantly eliminated the nephrotoxicity induced by OTA. Contrary, knock-down of ERK1/2 instead of p38 by their specific siRNA significantly eliminated the immunotoxicity induced by OTA. The observed effects indicate that OTA induced nephrotoxicity by p38 signaling pathway in PK15 cells and immunotoxicity by ERK signaling pathway in porcine primary splenocytes.