Naslov
Ochratoxin A induces apoptosis in kidney cells

Autori
Žanić-Grubišić, Tihana ; Čepelak, Ivana ; Petrik, Jozsef ; Rumora, Lada

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Apoptosis World 2008 From mechanisms to applications : Book of Abstracts / - , 2008, 245-245

Skup
Apoptosis World 2008 From mechanisms to applications

Mjesto i datum
Luksemburg, 23.01.2008. - 26.01.2008

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Ochratoxin A; Apoptosis; Kidney cells

Sažetak
Ochratoxin A (OTA) is a nephrotoxic, hepatotoxic, immunosuppressive, genotoxic and carcinogenic mycotoxin produced by storage moulds on a variety of foodstuffs. OTA has been implicated in the ethiology of Balkan endemic nephropathy (BEN). Chemical stability against heat and during industrial food processing makes OTA one of the most abundant mycotoxins present in cereals, coffee, beer, vine, meat products etc. We found that treatment with OTA was related to substantial disturbances in cellular signalling, and cell viability. In the experiments with MDCK, LLC-PK1 kidney cell lines we observed anti-mitotic effects of OTA. Cells undergoing apoptosis were identified by morphological changes (haematoxylin/eosin staining and TUNEL reaction), as well as, by biochemical markers of apoptotic pathways (MAPKs, caspases and HSPs). 5 μ M OTA treatment markedly reduced cell viability and induced apoptosis in 30, 8 % cells following 48 hrs of OTA treatment. We observed short and transient activation of ERK and strong activation of JNK and p38. Moreover, no changes in the Hsp70 and Hsp27 were detected, although cells were seriously injured, as seen from the reduced cell viability and increased release of LDH. Both cell lines were capable of having HSP70 induced following a heat shock. However, exposure to OTA before the heat shock challenge prevented Hsp70 induction. The absence of Hsp70 chaperone protection might contribute to the cumulative nephrotoxic effects of OTA, as seen in BEN. Absence of Hsp70 induction in liver and kidney was observed in vivo, in rats exposed to chronic treatment with 120 μ g OTA/kg b.w. We detected cell shrinkage, chromatin condensation and largely increased number of apoptotic cells in proximal tubules. Increased level of lipid peroxides and decreased activity of superoxide dismutase were indicative of disturbance in antioxidant status. We suggest that inhibition of defence mechanisms and development of oxidative stress are important elements in the mechanism of OTA toxicity.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA