Urine Ochratoxin A and Sphinganine/Sphingosine Ratio in Residents of the Endemic Nephropathy Area in Croatia

Abstract

The most plausible theory of the aetiology of endemic nephropathy links it with exposure to nephrotoxic mycotoxin ochratoxin A (OTA). In this study, the concentration of OTA and sphinganine/sphingosine (Sa/So) ratio, the biomarker of another nephrotoxic mycotoxin fumonisin B 1 exposure, were analysed in 45 human urine samples collected in the endemic village of Kaniža in Croatia and in 18 samples from control village. Samples were collected twice from the same persons in 2000 and 2005. In both years the frequency of OTA-positive samples was higher in Kaniža (43 % and 18 %, respectively) than in the control village (28 % and 6 %, respectively). OTA concentrations in samples collected in Kaniža were higher in 2000 than in 2005 (p<0.005). Although in both years Sa/So ratio was higher in Kaniža, the difference from the control group was not statistically signifi cant. No control sample contained OTA and had the Sa/So ratio >1 at the same time, while in Kaniža four such samples were collected in 2000 and one in 2005.

Ochratoxin A and Human Health Risk: A Review of the Evidence

“…Upon comparison, the levels of OTA found in urine in the Gilbert study ranged from non-detectable to 0.06 ng/ml: much lower than the 3.09 ng/ml mean urinary OTA level found in the nephritic syndrome patients in Wafa et al (1998). In both the Wafa et al (1998) and Gilbert et al (2001) studies, as well as the Croatian study in the systematic review (Domijan et al 2009), OTA presence was determined and analyzed by HPLC. Urinary OTA levels in humans from several different world regions, summarized in Table 3, range from <0.01-148 ng/ml.…”

“…Each study also had at least one corresponding control group. Domijan et al (2009) compared individuals in a BEN-endemic village to those in a non-BEN-endemic village, whereas Nikolov et al (2002) and Wafa et al (1998) study used healthy human controls. Epidemiological studies were not included in the review if they did not examine both cases (i.e., those with confirmed disease) and controls.…”

Aflatoxin, fumonisin, ochratoxin, zearalenone and deoxynivalenol biomarkers in human biological fluids: A systematic literature review, 2001–2018

“…Molecular biomarkers of mycotoxins such as mycotoxin metabolites or mycotoxin bioconjugated forms are used to measure human exposure and were used to assess the relationship between mycotoxin exposure and development of disease (Sangare-Tigori et al 2006;Grosso et al 2003;Hassen et al 2004;Zaied et al 2011;Domijan et al 2009;Ozcelik et al 2001;Brewer et al 2013).…”

Evaluating Weight of Evidence in the Mystery of Balkan Endemic Nephropathy

“…The health outcomes for AA are specific to the urinary systems in humans AA has been associated with other adverse health outcomes such as ESRD, UTTs, and other transitional cell carcinomas (5,69) The health outcomes for AA are specific to the urinary systems in humans OTA has been associated with other adverse health outcomes such as ESRD, UTTs, nephritic syndrome, and other transitional cell carcinomas (118,126) The health outcomes for PAHs are not specific to BEN PAHs such as pyrene, naphthalene, fluorine, and phenanthrene, which have been discovered in well water associated with Pliocene lignoites, have been associated with other adverse health outcomes; these outcomes include hemolytic anemia, kidney damage, liver damage, and jaundice, among others (130) The health outcomes for bacteria and viruses are not specific to BEN Leptospira infections, coronaviruses, and papova viruses have all been associated with other adverse health endpoints other than BEN (129,131) High (86) Higher levels of OTA in blood and urine in BEN patients compared to healthy individuals (89) No dose-response data exists in humans Higher levels of PAHs in BEN-endemic areas compared to nonendemic areas (33) No dose-response data exists in humans (5) Mutations in p53 tumor suppressor gene (5) 78% A:T to T:A mutation rate in tumors (5) OTA promotes adduct formation and increase DNA mutations (7) No specific mechanism proposed due to variety of PAHs found in water contaminated from Pliocene coal Laboratory evidence exists for animals; epidemiologic evidence exists for humans exposed to AA (69) Laboratory evidence exists for animals; (44) epidemiologic evidence exists for humans exposed to OTA (118,155) Only epidemiologic evidence exists correlating Pliocene coals, PAHs, and BEN (30,32) Varied laboratory data on animals exists; epidemiologic evidence shows some correlations between BEN and viruses/bacteria (6,22,157) High…”