hrvatski

Biokemijski mehanizmi nefrotoksičnosti mikotoksina

Mycotoxins are the secondary metabolites produced by several species of fungi that contaminate food of plant and animal origin. They are exceptionally stable and accumulate in human and animal tissues. Kidney is the main target organ for toxic effects of ochratoxin A (OTA), citrinin, vomitoxin and zearalenone. These mycotoxins can also be the hepatotoxic, genotoxic and carcinogenic agents, and they affect normal immune response. Etiology and the mechanism of development of endemic nephropathy development and approximately 50% other tubulointerstitial nephrites are not completely understood. Based on numerous studies of mycotoxin toxicity, especially OTA, their significant role in the etiologic mosaic of mentioned diseases has been assumed. Moreover, vomitoxin can cause glomeroulonefritis by inducing dysregulation of IgA production. At the cellular level, concentration-dependent effects of mycotoxins have been observed: induction the reactive oxygen species and cytokines production, enhancement of endunuclease and caspases activities and DNA adduct formation, stimulation of apoptosis, modulation of cell proliferation and inhibition of the transport systems for the organic anions and cations as well as inhibition of protein and DNA synthesis. In our extensive in vivo and in vitro studies of nephrotoxic effects of OTA, we examined some of these effects in Wistar rats exposed to very low OTA concentrations (120 mg OTA/kg body weight daily) for 60 days. OTA treatment caused an increase in the number of apoptotic epithelial renal cells. DNA analysis did not show characteristic fragmentation (DNA laddering). The apoptotic cells were visualised using TUNEL (Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay and were stained with haematoxylin and eosin in situ. The number of apoptotic cells in OTA treated rats for 10, 30 and 60 days increased 5-, 6.4- and 12.7 fold, respectively, as compared to control cells. The concentration of lipid peroxides showed an increase (36%), however, SOD activity decreased (26%) in rats treated for 60 days. The results of this study showed that the processes stimulating apoptosis and oxidative stress in renal cells could be activated by exposure to even very low concentrations of OTA.

oksidacijski stres; apoptoza; nekroza; mikotoksin; nefrotoksičnost

nije evidentirano

engleski

Biochemical mechanisms of mycotoxin nephrotoxicity

Mycotoxins are the secondary metabolites produced by several species of fungi that contaminate food of plant and animal origin. They are exceptionally stable and accumulate in human and animal tissues. Kidney is the main target organ for toxic effects of ochratoxin A (OTA), citrinin, vomitoxin and zearalenone. These mycotoxins can also be the hepatotoxic, genotoxic and carcinogenic agents, and they affect normal immune response. Etiology and the mechanism of development of endemic nephropathy development and approximately 50% other tubulointerstitial nephrites are not completely understood. Based on numerous studies of mycotoxin toxicity, especially OTA, their significant role in the etiologic mosaic of mentioned diseases has been assumed. Moreover, vomitoxin can cause glomeroulonefritis by inducing dysregulation of IgA production. At the cellular level, concentration-dependent effects of mycotoxins have been observed: induction the reactive oxygen species and cytokines production, enhancement of endunuclease and caspases activities and DNA adduct formation, stimulation of apoptosis, modulation of cell proliferation and inhibition of the transport systems for the organic anions and cations as well as inhibition of protein and DNA synthesis. In our extensive in vivo and in vitro studies of nephrotoxic effects of OTA, we examined some of these effects in Wistar rats exposed to very low OTA concentrations (120 mg OTA/kg body weight daily) for 60 days. OTA treatment caused an increase in the number of apoptotic epithelial renal cells. DNA analysis did not show characteristic fragmentation (DNA laddering). The apoptotic cells were visualised using TUNEL (Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay and were stained with haematoxylin and eosin in situ. The number of apoptotic cells in OTA treated rats for 10, 30 and 60 days increased 5-, 6.4- and 12.7 fold, respectively, as compared to control cells. The concentration of lipid peroxides showed an increase (36%), however, SOD activity decreased (26%) in rats treated for 60 days. The results of this study showed that the processes stimulating apoptosis and oxidative stress in renal cells could be activated by exposure to even very low concentrations of OTA.

oxidative stress; apoptosis; necrosis; mycotoxin; nephrotoxicity

nije evidentirano