Biomonitoring and risk assessment of human exposure to triazole fungicides.

Risk assessment and biomarkers were evaluated in volunteers exposed to triazole fungicides in southern Minas Gerais, Brazil. Volunteers were divided into two groups: occupationally and environmentally exposed to pesticides (n = 140) and those unexposed (n = 50) from urban areas. Urine samples were analyzed by GC-MS for triazoles, and samples from men and women in the exposed group were quantified. Groups were further stratified by sex to evaluate the biomarkers results. Oxidative stress was indicated by biomarker analysis for occupationally exposed men with elevated malondialdehyde levels and reduced superoxide dismutase and catalase activity (p < 0.0001). Bile acid levels were also elevated in the exposed group (p < 0.0001). Biomarkers in this study suggest recent, reversible changes due to pesticide exposure. Liver enzyme levels showed no significant differences. The highest Estimated Daily Intake for epoxiconazole ranged from 0.534 to 6.31 µg/kg-bw/day for men and 0.657-8.77 µg/kg-bw/day for women in the exposed group. Considering the highest detected urinary triazole value, the calculated Hazard Quotient for epoxiconazole was 0.789 for men and 1.1 for women. Results indicate a health risk associated with environmental triazole exposure, highlighting the importance of biomonitoring in risk assessment to prevent intoxication and assist in mitigating adverse health effects from chronic pesticide exposure.

Assessment of cellular damage with cytome assay among environmental/occupational triazole.

The use of triazole fungicides is common in Minas Gerais, Brazil. However, the risk arising from excessive and often unprotected exposure can be harmful to farmers. Therefore, we evaluated volunteers, exposed to triazole fungicides for cellular damage caused by this pesticide. In the buccal micronucleus cytome assay (BMCyt), cells were analyzed. Urinary triazoles were analyzed by the Liquid-Liquid Extraction coupled with Gas-chromatography/mass-spectrometry (LLE-GC/MS). Statistical differences were found for all cell types evaluated in residents of rural areas (n = 145). Analysis of variance showed statistical difference in kariolytic and pyknotic cells, between the groups of men and women living in rural areas, with higher incidence in the male group. Likewise, higher concentrations triazoles in urine samples in the male group were observed. Greater cellular damage suggests increases in DNA damage, chromossomal instability and cell deaths. The results showed the urgency of the public management with the implementation of measures to minimize the pesticides exposure.

Pharmacological potential of new metronidazole/eugenol/dihydroeugenol hybrids against Trypanosoma cruzi in vitro and in vivo.

AIMS: From well-delimited immunomodulatory, redox and antimicrobial properties; metronidazole and eugenol were used as structural platforms to assembly two new molecular hybrids (AD06 and AD07), whose therapeutic relevance was analyzed on T. cruzi infection in vitro and in vivo. METHODS: Non-infected, T. cruzi-infected H9c2 cardiomyocytes, and mice non-treated and treated with vehicle, benznidazole (Bz - reference drug), AD06 and AD07 were investigated. Parasitological, prooxidant, antioxidant, microstructural, immunological, and hepatic function markers were analyzed. RESULTS: Our findings indicated that in addition to having a direct antiparasitic effect on T. cruzi, metronidazole/eugenol hybrids (especially AD07) attenuated cellular parasitism, reactive species biosynthesis and oxidative stress in infected cardiomyocytes in vitro. Although AD06 and AD07 exerted no relevant impact on antioxidant enzymes activity (CAT, SOD, GR and GPx) in host cells, these drugs (especially AD07) attenuated trypanothione reductase activity in T. cruzi, which increased parasite's susceptibility to in vitro pro-oxidant challenge. AD06 and AD07 were well tolerated and do not determine humoral response suppression, mortality (100 % survival) or hepatotoxicity in mice, as indicated by transaminases plasma levels. AD07 also induced relevant in vivo antiparasitic and cardioprotective effects, attenuating parasitemia, cardiac parasite load and myocarditis in T. cruzi-infected mice. Although this cardioprotective response is potentially related to AD07 antiparasitic effect, a direct anti-inflammatory potential of this molecular hybrid cannot be ruled out. CONCLUSION: Taken together, our findings indicated that the new molecular hybrid AD07 stood out as a potentially relevant candidate for the development of new, safe and more effective drug regimens for T. cruzi infection treatment.