SCIENTIFIC REPORT ON THE OCCURENCE OF ARISTOLOGIC ACID AS A CAUSE OF ENDEMIC NEPHROPATHY IN REPUBLIC OF CROATIA
Creators: name: CROATIAN AGENCY FOR AGRICULTURE AND FOOD
Publisher: name: Zenodo
Year: 2022
Subjects: endemic nephropathy
aristolochic acid
cereals
occurence
Croatia

description: Aristolochic acid includes a group of naturally occurring nitro phenanthrene carboxylic acids, but usually this refers to aristolochic acid I (AA I) and aristolochic acid II (AA II). It could be found in the stem and seeds of plants from the genus Aristolochia spp., which are widespread all over the world. It is believed that aristolochic acid is responsible for the development of endemic nephropathy (EN). This is a chronic tubulointerstitial nephropathy in humans, which is clinically manifested by terminal renal failure after an asymptomatic period of several years. Aristolochic acid is proven to be nephrotoxic, mutagenic and carcinogenic. Characteristically it affects two target tissues: cells of the proximal renal tubule and urothelial cells. In 2012. The International Agency for Research on Cancer (IARC) classified aristolochic acid in group 1, i.e. as a human carcinogen, because there were sufficient evidence that it causes cancer of the renal tubule and ureter. On the territory of the Republic of Croatia, more precisely in west Brod of Posavina, a focus of endemic nephropathy was found. Since there is a lack of data on the exposure of the population of the Republic of Croatia to aristolochic acid, especially the population in the endemic area, the Scientific Panel on Chemical Hazards of the Croatian Food Agency (now the Croatian Agency for Agriculture and Food) proposed a three-year research study entitled "Citrinine and aristolochic acid as cereal contaminants and potential agent of endemic nephropathy" in cereals (wheat, barley, corn) in four Croatian counties (Brod-Posavina, Osijek-Baranja, Koprivnica-Križevci and Međimurje). The results of the research were used for preparation of this scientific report. The research results show a very high percentage of samples with the concentration of AA I below the limit of quantification (LOQ), and only 4,17% of the samples were above the LOQ in concentration ranging from 1.36 mg/kg to 93 mg/kg. Also, in this research a sample contaminated with AA II with a concentration higher than the LOQ (1 mg/kg) was not found. By comparing the results of the concentration of aristolochic acid in samples collected in 2017, 2018 and 2019, no statistically significant difference in the concentration of aristolochic acid I (p=0.25) was found. Furthermore, the statistical analysis found that there is no statistically significant difference between the contamination of different types of cereals (p=0.4953), as well as that there is no statistically significant difference in the distribution of positive samples by county (p=0.65). Statistical data analysis was performed using Statistics 13.3. software package. Therefore, the results of this research indicate that the occurrence of aristolochic acid I (AA I) cannot be associated with endemic nephropathy in the Republic of Croatia and the contamination of cereals with aristolochic acid I and II does not pose a health risk for humans.
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