Toxins | |
Apoptosis Induction by OTA and TNF-α in Cultured Primary Rat Hepatocytes and Prevention by Silibinin | |
Ebtisam Essid1  Yousef Dernawi2  | |
[1] Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus-Liebig-University Giessen, Schubert Street 81, Giessen D-35392, Germany;Institute of Pathology, Faculty of veterinary Medicine, Justus-Liebig-University Giessen, Frankfurter Street 96, Giessen D-35392, Germany; | |
关键词: ochratoxin A; tumor necrosis factor alpha; UV-C light; hydrogen peroxide; rat hepatocytes; DNA ladder; caspase-3; apoptosis; malondialdehyde; silibinin; | |
DOI : 10.3390/toxins4111139 | |
来源: mdpi | |
【 摘 要 】
In cultures of primary rat hepatocytes, apoptosis occurred after application of 20 ng/mL tumor necrosis factor alpha (TNF-α). However, this was only in the presence of 200 ng/mL of the transcriptional inhibitor actinomycin D (ActD). This toxic effect was completely prevented in the presence of 25 µg/mL soluble TNF-α receptor I (sTNFR I) in the supernatant of hepatocyte cell cultures. Apoptosis also occurred after application of 12.5 µmol/L ochratoxin A (OTA). However, that was not prevented by up to 500 µg/mL sTNFR I, indicating that TNF-α/TNFR I is not involved in OTA mediated apoptosis in hepatocytes. The antioxidative flavanolignan silibinin in doses from 130 to 260 µmol/L prevented chromatin condensation, caspase-3 activation, and apoptotic DNA fragmentation that were induced by OTA, by 10 mmol/L hydrogen peroxide (H2O2) and by ultraviolet (UV-C) light (50 mJ/cm2), respectively. To achieve protection by silibinin, the drug was applied to the cell cultures for 2 h in advance. OTA stimulated lipid peroxidation on cultured immortalized rat liver HPCT cells, as was revealed by malondialdehyde (MDA) production. Lipid peroxidation occurred further by H2O2 and ActD/TNF-α incubation. These reactions were also suppressed by silibinin pretreatment. We conclude that the anti-apoptotic activity of silibinin against OTA, H2O2 and ActD/ TNF-α is caused
【 授权许可】
CC BY
© 2012 by the authors; licensee MDPI, Basel, Switzerland.
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