Early cytotoxic and genotoxic effects of atrazine on Wistar rat liver: A morphological, immunohistochemical, biochemical, and molecular study

被引:74
作者
Campos-Pereira, Franco D. [1 ]
Oliveira, Camila A. [1 ]
Pigoso, Acacio A. [1 ]
Silva-Zacarin, Elaine C. M. [2 ]
Barbieri, Renata [1 ]
Spatti, Erika F. [1 ]
Marin-Morales, Maria A. [3 ]
Severi-Aguiar, Grasiela D. C. [1 ]
机构
[1] UNIARARAS, Ctr Univ Herminio Ometto, Programa Posgrad Ciencias Biomed, BR-13607339 Sao Paulo, Brazil
[2] Univ Fed Sao Carlos, UFSCAR, Lab Biol Estrutural & Func LABEF, BR-18052780 Sao Paulo, Brazil
[3] Univ Estadual Paulista, UNESP, Inst Biociencias, Dept Biol, BR-13506900 Sao Paulo, Brazil
关键词
Atrazine; Cytotoxicity; Oxidative stress; Antioxidant enzyme expression; Connexins; Heat shock proteins; TOXICITY; EXPOSURE; HERBICIDE; APOPTOSIS; RISK;
D O I
10.1016/j.ecoenv.2011.11.020
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
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 400 mg/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. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:170 / 177
页数:8
相关论文
共 33 条
[1]   A REVIEW OF THE COORDINATED RESEARCH EFFORT ON THE COMPARISON OF TEST SYSTEMS FOR THE DETECTION OF MUTAGENIC EFFECTS, SPONSORED BY THE EEC [J].
ADLER, ID .
MUTATION RESEARCH, 1980, 74 (02) :77-93
[2]  
[Anonymous], 1974, Catalase. Methods Enzym. Anal., DOI DOI 10.1016/B978-0-12-091302-2.50032-3
[3]   Ameliorative action of melatonin on oxidative damage induced by atrazine toxicity in rat erythrocytes [J].
Bhatti, J. S. ;
Sidhu, I. P. S. ;
Bhatti, G. K. .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 2011, 353 (1-2) :139-149
[4]   An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans [J].
Bonassi, Stefano ;
Znaor, Ariana ;
Ceppi, Marcello ;
Lando, Cecilia ;
Chang, Wushou Peter ;
Holland, Nina ;
Kirsch-Volders, Micheline ;
Zeiger, Errol ;
Ban, Sadayuki ;
Barale, Roberto ;
Bigatti, Maria Paola ;
Bolognesi, Claudia ;
Cebulska-Wasilewska, Antonina ;
Fabianova, Eleonora ;
Fucic, Alexandra ;
Hagmar, Lars ;
Joksic, Gordana ;
Martelli, Antonietta ;
Migliore, Lucia ;
Mirkova, Ekaterina ;
Scarfi, Maria Rosaria ;
Zijno, Andrea ;
Norppa, Hannu ;
Fenech, Michael .
CARCINOGENESIS, 2007, 28 (03) :625-631
[5]   Ecological relevance and sensitivity depending on the exposure time for two biomarkers [J].
Campero, Melina ;
Ollevier, Frans ;
Stoks, Robby .
ENVIRONMENTAL TOXICOLOGY, 2007, 22 (06) :572-581
[6]   In vivo genotoxicity evaluation of atrazine and atrazine-based herbicide on fish Carassius auratus using the micronucleus test and the comet assay [J].
Cavas, Tolga .
FOOD AND CHEMICAL TOXICOLOGY, 2011, 49 (06) :1431-1435
[7]  
EPA U.S, 1989, DRINK WAT HLTH ADV P, P43
[8]   Heat shock proteins: Endogenous modulators of apoptotic cell death [J].
Garrido, C ;
Gurbuxani, S ;
Ravagnan, L ;
Kroemer, G .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 286 (03) :433-442
[9]  
HALLIWELL B, 2007, FREE RADICAL BIO MED, P79
[10]  
Hermes-Lima M., 2004, Functional metabolism: regulation and adaptation, P319, DOI DOI 10.1002/047167558X.CH12