Assessment of Exposure to Mycotoxins in Spanish Children through the Analysis of Their Levels in Plasma Samples.

In this study, we present, for the first time in Spain, the levels of 19 mycotoxins in plasma samples from healthy and sick children (digestive, autism spectrum (ASD), and attention deficit hyperactivity (ADHD) disorders) (n = 79, aged 2-16). The samples were analyzed by liquid chromatography-mass spectrometry (triple quadrupole) (LC-MS/MS). To detect Phase II metabolites, the samples were reanalyzed after pre-treatment with ß-glucuronidase/arylsulfatase. The most prevalent mycotoxin was ochratoxin A (OTA) in all groups of children, before and after enzyme treatment. In healthy children, the incidence of OTA was 92.5% in both cases and higher than in sick children before (36.7% in digestive disorders, 50% in ASD, and 14.3% in ADHD) and also after the enzymatic treatment (76.6 % in digestive disorders, 50% in ASD, and 85.7% in ADHD). OTA levels increased in over 40% of healthy children after enzymatic treatment, and this increase in incidence and levels was also observed in all sick children. This suggests the presence of OTA conjugates in plasma. In addition, differences in OTA metabolism may be assumed. OTA levels are higher in healthy children, even after enzymatic treatment (mean OTA value for healthy children 3.29 ng/mL, 1.90 ng/mL for digestive disorders, 1.90 ng/mL for ASD, and 0.82 ng/mL for ADHD). Ochratoxin B appears only in the samples of healthy children with a low incidence (11.4%), always co-occurring with OTA. Sterigmatocystin (STER) was detected after enzymatic hydrolysis with a high incidence in all groups, especially in sick children (98.7% in healthy children and 100% in patients). This supports glucuronidation as a pathway for STER metabolism in children. Although other mycotoxins were studied (aflatoxins B1, B2, G1, G2, and M1; T-2 and HT-2 toxins; deoxynivalenol, deepoxy-deoxynivalenol, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol; zearalenone; nivalenol; fusarenon-X; neosolaniol; and diacetoxyscirpenol), they were not detected either before or after enzymatic treatment in any of the groups of children. In conclusion, OTA and STER should be highly considered in the risk assessment of mycotoxins. Studies concerning their sources of exposure, toxicokinetics, and the relationship between plasma levels and toxic effects are of utmost importance in children.

[High levels of sterigmatocystin in patients with chronic liver diseases]. / Detectarea sterigmatocistinei la pacientii cu boala ii hepatica cronica.

UNLABELLED: Sterigmatocystin (STC) is a wide spread mycotoxin produced by Aspergillus fungi, with hepatotoxic and carcinogenetic proprieties. OBJECTIVES: To determine the STC concentration in blood and urine from patient with liver cirrhosis (LC) and hepatocellular carcinoma (HCC), with correlation with liver function parameters. MATERIAL AND METHODS: The study enrolled 166 patients divided in three groups: control--55 patients (27M, 28F); LC--58 patients (31M, 27F); HCC--53 patients (26M, 27F). 20 ml of blood and 50 ml of urine were collected from each patient and liver enzymes and alfa-fetoprotein (AFP) were measured. STC was determined by high performance liquid chromatography, with concomitant detection in ultraviolet and fluorescence. RESULTS: STC was detected in 26.2% of samples, more frequently in LC and HCC groups (p < 0.001). STC mean values were 0.014 ng/ml and 0.005 ng/ml in blood, respective urine of controls, rising to 0.626 ng/ml (p = 0.003) respective 1.053 ng/ml (p = 0.049) in LC and 2.02 ng/ml in blood (p < 0.0001) and 9.39 ng/ml in urine (p = 0.003) in patients with HCC. There is a perfect correlation between serum and urinary levels of STC in controls (r = 1), that become weak in patients with LC (r = 0.48) and insignificant in HCC (r = 0.15). AFP values were significantly correlated with STC concentration in patient with HCC, in both blood (r = 0.31) and urine (r = 0.84). CONCLUSIONS: STC values in patients with LC and HCC were significantly higher compared to controls. Strong positive correlation of STC with AFP in patients with liver cancer suggested a possible role of this mycotoxin in pathogenesis of the disease.

[High blood and urine concentration of hepatotoxic mycotoxins (aflatoxin B1, sterigmatocystin) in patients with liver cirrhosis]. / Detectarea micotoxinelor hepatotoxice la pacienti cu ciroza Hepatica.

UNLABELLED: Aflatoxins and sterigmatocystin are potent carcinogens, certainly involved in pathogenesis of liver cancer. AIM: To evaluate the risk of mycotoxin intake and to determine the presence of aflatoxin B1 (AFB1) and sterigmatocystin (STC) in patients with liver cirrhosis. MATERIAL AND METHOD: The study included 92 patients (33 controls, 59 liver cirrhosis) that completed a food frequency questionnaire (FFQ). Blood and urine samples were collected and mycotoxins determined by high performance liquid chromatography. RESULTS: 18.18% samples in controls and 72.88% in cirrhosis group presented detectable levels of mycotoxins. The mean values of AFB1 in blood were 0.7 ng/mL in controls and 1.67 ng/mL in test group (p = 0.11); STC presented 60 times higher levels in second group (p < 0.01). AFB1 presented a mean level of 1.2 ng/mL in urine of test group (not detected in controls); STC presented 256 time higher concentration in urine of cirrhotic patients, with a perfect correlation between blood and urine levels in control (r=1) and no correlation in test group (r = 0.05). There were no correlations between mycotoxin, liver enzymes, alpha-fetoprotein and mycotoxin intake risk estimated by FFQ. CONCLUSION: Most of the patients presented detectable levels of mycotoxins, significantly increased in cases with liver cirrhosis, probable due to a specific metabolic pattern.