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2021, vol. 71, br. 6, str. 491-507
Delovanje mankozeba kao endokrinog ometača
aIM Sechenov First Moscow State Medical University, Moscow, Russia + Peoples' Friendship University of Russia (RUDN University), Moscow, Russia + Orenburg State University, Institute of Bioelementology, Orenburg, Russia
bIM Sechenov First Moscow State Medical University, Moscow, Russia + Albert Einstein College of Medicine, Department of Molecular Pharmacology, Bronx, New York, United States of America
cAlbert Einstein College of Medicine, Department of Molecular Pharmacology, Bronx, New York, United States of America
dInstituto Nacional de Neurología y Neurocirugía, Laboratorio de Aminoácidos Excitadores/Laboratorio de Neurofarmacología Molecular y Nanotecnología, Mexico City, Mexico
eIM Sechenov First Moscow State Medical University, Moscow, Russia
fGolikov Research Center of Toxicology, Saint Petersburg, Russia
gGuangxi Medical University, School of Public Health, Department of Toxicology, Nanning, China
hUniversidade Federal de Santa Maria, Departamento de Bioquímica e Biologia Molecular, CCNE, Santa Maria, Rio Grande do Sul, Brazil
iPeoples' Friendship University of Russia (RUDN University), Moscow, Russia + Orenburg State University, Institute of Bioelementology, Orenburg, Russia + Yaroslavl State University, Yaroslavl, Russia

e-adresatinkov.a.a@gmail.com
Projekat:
MA was supported in parts by a grant from the National Institute of Environmental Health Science (NIEHS) R01 ES10563
JBTR is a recipient of CNPq fellowship and CAPES-PROEX-EPIDEMIAS09 grant
The study was performed with the support of the Russian Ministry of Science and Higher Education, Project № 0856-2020-0008

Sažetak
Ovo istraživanje je imalo za cilj da pruži pregled postojećih podataka o mehanizmima uključenim u delovanje mankozeba (MCZ) kao endokrinog ometača u ciljnim organima, u koja se ubrajaju štitna i polne žlezde, kao i u ostalim endokrinim tkivima na koja potencijalno može uticati MCZ. Pokazalo se da izloženost mankozebu remeti rad štitne žlezde tako što ometa sintezu tiroidnih hormona inhibirajući aktivnost natrijum-jodid simportera (NIS) i tiroidne perioksidaze (TPO), kao i ekspresiju tiroglobulina. Neposredno tirotoksično dejstvo takođe može doprineti razvoju tiroidne patologije pri izlaganju mankozebu. Delovanje mankozeba na polne žlezde uključuje inhibiciju sinteze polnih steroida usled inhibicije P450scc (CYP11A1), kao i 3b-HSD i 17b-HSD. Uporedo sa promenama u sintezi hormona, pokazalo se da MCZ snižava slanje signala androgenih i estrogenih receptora. Ovi efekti koji se odnose na polne žlezde zajedno dovode do pojave reproduktivne disfunkcije kako kod muškaraca, tako i kod žena. Pored jasno utvrđenih ciljnih organa na koja MCZ deluje kao endokrini ometač, mogu biti pogođena i druga endokrina tkiva. Konkretno, pokazalo se da ovaj fungicid utiče na sintezu kortizola, moguće posredstvom modulacije aktivnosti CYP11B1. Pored toga, utvrđeno je da izloženost mankozebu remeti signale PPARg, koji su ključni regulator adipogeneze. Postojeći podaci takođe ukazuju na to da do posledica izloženosti mankozebu može doći posredstvom modulacije ose hipotalamus-hipofizaciljni organ. Navodi se da je moguće da neurotoksičnost mankozeba makar delimično utiče na centralne mehanizme rada endokrinog sistema. Ipak, neophodna su dalja istraživanja kako bi se razjasnili ne samo mehanizmi delovanja mankozeba kao endokrinog ometača već i njegova toksičnost uopšte.
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O članku

jezik rada: engleski
vrsta rada: pregledni članak
DOI: 10.5937/arhfarm71-34359
objavljen u SCIndeksu: 29.12.2021.
metod recenzije: jednostruko anoniman
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