022-0222148-2142 Toxic Effects of Mycotoxins on Humans and Animals

MINISTRY OF SCIENCE, EDUCATION AND SPORTS OF THE REPUBLIC OF CROATIA (2007-2014)

Principal Investigator: Maja Peraica

SUMMARY
Mycotoxins are the metabolites of moulds with toxic, carcinogenic, genotoxic, mutagenic, and teratogenic properties. In our earlier studies, we found low concentrations of fumonisin B1 (FB1), fumonisin B2, ochratoxin A (OTA), and zearalenon in food samples collected in various regions of Croatia. OTA is considered to be involved in the development of endemic nephropathy (EN). This kidney disease of unknown etiology and high frequency of tumors of the upper urothelial tract appears in the western part of Brodska Posavina. It is speculated that, in addition to OTA, another nephrotoxic mycotoxin such as FB1 should be involved in the development of EN.
The mechanism of the toxicity of OTA and FB1 is not fully understood. It was proved on cultured cells that OTA and FB1 cause oxidative damage of lipids and DNA. However, it is not know whether low concentrations of these mycotoxins usually found in food can also cause oxidative damage of lipids, proteins and DNA in experimental animals. OTA and FB1 are frequently found together in cereals, and therefore it would be important to see whether their effect is synergistic or not. OTA is an organic anion that accumulates in the kidney cells and partially excretes in urine. OTA is partially reabsorbed due to organic anion transporters (OAT) on the epithelial cells along the nephron, which may contribute to its toxicity in specific parts of the kidney. Recent investigations have shown that the localization of specific OATs in rats is sex-related. Toxic effects of OTA are more severe in male rats, which could be due to the higher expression of OAT in males.
The proposed project will use recently developed methods, some of which will be used for the first time in the research of the mechanisms of action of mycotoxins.
The aim of this project is to clarify the role of oxidative stress caused by mycotoxins in damage of macromolecules (DNA, lipids, and proteins), as well as to improve the understanding of the mechanism of toxicity of OTA by investigating the changes in kidney OAT system. The other aim is to find out whether exposure to OTA and FB1 is involved in the development of EN.
We expect that our results will: a) show whether oxidative stress is involved in the mechanism of OTA and FB1 toxicity, and whether this effect is synergistic, b) show whether OTA affects the expression of OATs in the rat kidney and whether this effect is sex-related, and c) improve the knowledge about the mechanism of EN development.