Naslov
Mechanisms of mycotoxine toxicity

Autori
Žanić-Grubišić, Tihana

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

Izvornik
Book of abstract Congress of the Croatian Society of Biochemistry and Molecular Biology on the occasion of the 30th Anniversary with international participation / Kovarik, Zrinka - Zagreb : Hrvatsko društvo za biokemiju i molekularnu biologiju (HDBMB), 2006

Skup
Congress of the Croatian Society of Biochemistry and Molecular Biology on the occasion of the 30th Anniversary with international participation

Mjesto i datum
Vodice, Hrvatska, 03.10.2006. - 07.10.2006

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
Ochratoxin A; Mycotoxine; Apoptosis

Sažetak
Ochratoxin A (OTA) is a nephrotoxic, hepatotoxic, immunosuppresive, 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. OTA has slow metabolism and a long serum half-life. Several hypotheses have been proposed to explain mechanisms of OTA toxicity. Specific interferences with phenylalanine dependent metabolic reactions are related to Phe moiety of the OTA molecule. We observed OTA – induced inhibition of Phe - hydroxylase in liver, but not in kidney of OTA treated rats. Administration of Phe could generate reversal of this inhibition. Non-specific interactions are related to the OTA ability to disturb cellular signalling and influence cell cycle and 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 (hematoxylin/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. Activation of caspase-3 was not involved in the process. 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 bw. 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