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An expected multi-causal nature of spontaneous animal and human nephropathy in Bulgaria and South Africa

Final Activity Report Summary - CAUSE KIDNEY DAMAGE (An expected multi-causal nature of spontaneous animal and human nephropathy in Bulgaria and South Africa)

The most important scientific achievements made are:
1) A synergistic interaction was found between ochratoxin A (OTA), citrinin (CIT) and fumonisin B1 (FB1) in suppression of metabolic activity of PHA-stimulated peripheral blood mononuclear cells. There is not 'in vitro' synergistic effect between OTA and PA as measured by MTT assay, unlike the strong 'in vivo' synergistic effect between the same mycotoxins.

2) A new toxic metabolite with green fluorescence produced mainly by P. polonicum strain was found in almost all analysed feed samples from Bulgaria.

3) The pathomorphological comparison between mycotoxic porcine nephropathy ranged in Bulgaria and South Africa revealed that the kidneys from spontaneous cases of porcine nephropathy in Bulgaria can be divided into 5 separated groups, which illustrate the progressive stages of development of the disease ('mottled', 'enlarged and marbled', 'enlarged and pale', 'cystic' and 'fibrotic'), whereas the kidneys from spontaneous cases of porcine nephropathy in South Africa show macroscopic pattern characteristic only for the first three groups of this classification.

4) The real cause for the nephropathy observed in Bulgarian pigs and chicks as well as in South African pigs is already established:
a) Spontaneous nephropathy in Bulgaria, which is observed frequently during the meat inspection and which differs morphologically from the classical description of mycotoxic porcine/chicken nephropathy as made in Denmark was found to have multi-mycotoxic etiology being mainly provoked by combined effect of OTA, PA and FB1 in addition to not yet identified metabolite. A heavy contamination with Gibberella fujikuroi (F. verticillioides) and P. aurantiogriseum complex (mainly P. polonicum) was observed in almost all examined feed samples coming from pig- and chick farms with nephropathy problems from Bulgaria. In contrast, a light contamination with A. ochraceus, P. verrucosum and P. citrinum was observed in the same feed samples and these species were isolated as very rare component of the mycobiota.
b) Spontaneous nephropathy in pigs seen in South Africa was also found to have multi-mycotoxic etiology involving the same mycotoxins as Bulgarian nephropathy.

5) The cause of the differences in pathomorphological picture of various nephropathies in different countries was already found to be due to the different combination of various nephrotoxic mycotoxins in spontaneous contaminated feeds. The pathomorphological picture of both nephropathies in Bulgaria and South Africa was found to differ from the classical description of mycotoxic porcine nephropathy as made in Scandinavia by the extensive vascular changes.

6) A synergistic interaction was found between OTA and FB1 in addition to that between OTA and PA in 'in vivo' experiments.

7) Some protocols for the safe utilization of OTA-contaminated feeds were established in order to reduce farm losses from a decrease of weight gain and egg production in stock chicks and to avoid the rejection or condemnation of such feed. A real protective effect was found for the following feed additives: water extract of artichoke (WEA), sesame seed (SS), Roxazyme-G (RG) and phenylalanine (PHE) against the suppressive effect of OTA on egg production of laying hens in chronic experiments with chicks. A significant protection was found against the decrease of the weight or the quantity of eggs as well as against the delay of the beginning of the laying period of chicks, both of which were provoked by OTA. These protective effects were strongest in chicks treated with SS or WEA, but were slightest in chicks treated with PHE.

8) A protective effect of the same feed additives against the carcinogenic effect of OTA in chicks was also found. The number of OTA induced neoplasms was less in L-PHE treated group and no neoplasms were found in the groups treated with WEA, SS and RG. The target organs for carcinogenic effect of OTA in chicks were found to be kidneys and liver.