engleski

Mycotoxin theory of endemic nephropathy

Mycotoxin theory of endemic nephropathy (EN) was initially based on the similarities of pathological kidney lesions in patients with EN and that of pigs in Scandinavian countries suffering of nephropathy proven to be caused by mycotoxin ochratoxin A (OTA). The occurrence of EN in rural population of restricted areas without significant industry not only in Croatia, but also in Bosnia and Herzegovina, Bulgaria, Kosovo, Rumania, and Serbia indicates that some natural compound should be involved in the etiology of this disease. In Croatia, as well as in other countries with areas where EN is known the outbreak of the EN occurred in early seventies of the last century. About ten years later in the same areas high prevalence of urothelial tumors (UT) was noticed indicating that the same agent should be involved in the etiology of UT and EN. The appearance of EN in persons that have lived in endemic area for at least 10 years and left the area afterwards, indicates that the exposure to this natural toxin should be long. Although mycotoxin OTA was found in blood and in various commodities of inhabitants in endemic areas in Bulgaria and Croatia, several problems in proving that mycotoxin etiology of EN were encountered. Namely, food is never contaminated with a single mould, and mycotoxin-producing moulds may produce simultaneously various mycotoxins. The production of mycotoxins shows high seasonal variability depending on the local temperature and moisture variations. Mycotoxins are ubiquitous in the world, and OTA nephrotoxic and carcinogen mycotoxin that is the most suspected as the etiological factor in EN was found in low concentrations in blood of inhabitants in countries where EN is not present. However, this fact does not discard the mycotoxin theory of EN, because there is high probability that inhabitants in the area with EN are exposed also to other nephrotoxic mycotoxins such as fumonisins (particularly the most toxic and most frequently found fumonisin B1 - FB1) and citrinin. In Bulgarian studies citrinin was found more frequently and in higher concentrations in food of patients with EN than in healthy population. Extremely short half-life of FB1 in human blood makes the measurement of its concentration in human blood unreliable, and therefore its biomarkers (ratio of sphingolipids sphinganine and sphingosine) are measured. In one study performed in endemic area in Croatia, the concentration of these biomarkers was found to be higher in patients with EN and in persons “ at risk” than in control population. Data on cultured cells and on experimental animals have shown that the treatment either with FB1 or with citrinin together with OTA significantly increases toxicity and genotoxicity of OTA. The synergistic increase of genotoxicity was seen in kidney of experimental animals even at OTA and FB1 doses that are considered to be safe of humans. Unfortunately, until now there is no study on simultaneous human exposure to OTA and other mycotoxins.

endemic nephropathy; mycotoxins; ochratoxin A; fumonisin B1

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