title: Early cytotoxic and genotoxic effects of atrazine on Wistar rat liver: a morphological, immunohistochemical, biochemical, and molecular study.
abstract: Risk assessments suggest that intermediate and long-term exposure to triazine herbicides and its metabolites through water can cause severe damage to human health. The objective of this study was to investigate the possible effects of atrazine on Wistar rats submitted to subacute treatment. For this purpose, the activity of catalase and alanine aminotransferase was quantified, and the effect of the herbicide on cell membranes was examined based on the measurement of lipid peroxidation and consequent formation of malondialdehyde and on the mRNA expression of antioxidant enzymes (Mn-superoxide dismutase [SOD] and GSTM1) and connexins. In addition, we evaluated histopathological alterations in the liver, cellular expression of SOD and glutathione (GST), activation of heat shock proteins (HSPs) by immunohistochemistry, and the induction of apoptosis. The genotoxic potential of the herbicide was investigated by the micronucleus test in bone marrow smears. Adult male Wistar rats were treated with an aqueous solution of atrazine at a concentration of 400mg/kg/day, by gavage, for 14 consecutive days. Control groups were also included. The results showed an increase of catalase levels and maintenance of the expression of antioxidant enzymes (SOD and GST). In addition, lipid peroxidation, hepatic tissue degeneration, activation of HSP90, increased levels of connexin mRNA, and genotoxicity were observed. In conclusion, atrazine induced early hepatic oxidative stress that triggered defense mechanisms to maintain the morphophysiological integrity of the liver. Further studies are needed to better understand the effects of this herbicide on human health.
authors.affiliation: Programa de Pós-Graduação em Ciências Biomédicas, Centro Universitário Hermínio Ometto, UNIARARAS, Avenida Dr. Maximiliano Barutto, no 500, Jd. Universitário, CEP 13607-339 Araras, São Paulo, Brazil.
authors.forename: Franco D
authors.initials: FD
authors.lastname: Campos-Pereira
authors.forename: Camila A
authors.initials: CA
authors.lastname: Oliveira
authors.forename: Acácio A
authors.initials: AA
authors.lastname: Pigoso
authors.forename: Elaine C M
authors.initials: EC
authors.lastname: Silva-Zacarin
authors.forename: Renata
authors.initials: R
authors.lastname: Barbieri
authors.forename: Erika F
authors.initials: EF
authors.lastname: Spatti
authors.forename: Maria A
authors.initials: MA
authors.lastname: Marin-Morales
authors.forename: Grasiela D C
authors.initials: GD
authors.lastname: Severi-Aguiar
mesh_terms: D000818:Animals; D001280:Atrazine / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D003603:Cytotoxins / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006540:Herbicides / Q000378:metabolism / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D003603:Cytotoxins; D006540:Herbicides; D009153:Mutagens; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D005978:Glutathione; D001280:Atrazine