Romanian Society of Pharmaceutical Sciences
 

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EXPOSURE TO GLYPHOSATE AND ITS MIXTURE WITH DICAMBA AND 2,4-D FROM GESTATIONAL DAY 6 UNTIL WEANING IN RAT DAMS REVEALS SIGNS OF NON-ALCOHOLIC FATTY LIVER DISEASE

ANDREI EUGEN CIRSTEA 1#, ANCA OANA DOCEA 2, LILIANA CERCELARU 3#, ANDREI IOAN DROCAS 4#, RADU MITRUT 5*, ROBIN MESNAGE 6, CRISTINA MARGINEAN 7, DRAGOS GEORGE POPA 8, CRISTIAN MARINAȘ 9,10, KIRILL S GOLOKHVAST 11, ARISTIDIS TSATSAKIS 12, MICHAEL N ANTONIOU 6, ANDREEA LETIȚIA ARSENE 13, DANIELA CALINA 14

1Doctoral School, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania
2 Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania
3 Department of Anatomy and Embryology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
4 Department of Urology, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania
5 Department of Cardiology, University and Emergency Hospital, 050098, Bucharest, Romania
6 King's College London, Gene Expression and Therapy Group, Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, Guy's Hospital, London, SE1 9RT, United Kingdom
7 Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania
8 Department of Plastic Surgery, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania
9 Department of Obstetrics and Gynaecology, Emergency Clinical County Hospital, 200642, Craiova, Romania
10 Department of Human Anatomy, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania
11 Siberian Federal Scientific Centre for Agrobiotechnology RAS, Krasnoobsk, Russia
12 Center of Toxicology Science & Research, Medical School, University of Crete, 71003, Heraklion, Crete, Greece
13 “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 010458, Bucharest, Romania
14 Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania

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The growing usage of glyphosate, dicamba, and 2,4-D herbicide mixtures to combat glyphosate-resistant weeds raises concerns about human health and environmental consequences. The purpose of this study was to see how developmental exposure to glyphosate and a herbicide mixture combining glyphosate, dicamba, and 2,4-D affected rat dams' liver structure and function. A mixture of glyphosate, dicamba, and 2,4-D each at their European Union acceptable daily intake (ADI) (0.5, 0.002, and 0.3 mg/kg bw/day, respectively) and glyphosate at the ADI and NOAEL levels (0.5 and 50 mg/kg bw/day), were administered to pregnant Wistar rats from day-6 of gestation until weaning. The dams were sacrificed after weaning, and blood and liver tissue collected. In dams, glyphosate exposure resulted in the induction of non-alcoholic liver disease in a dose-dependent manner. In addition, exposure to the herbicide mixture resulted in effects similar to those observed with glyphosate at the NOAEL dose, suggesting at least an additive effect of the herbicide mixture at regulatory doses considered individually safe for humans.