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1.
Exp Toxicol Pathol ; 67(10): 525-32, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26310382

ABSTRACT

São Paulo state, Brazil, is one of the main areas of sugar cane planting in the world. Extensive use of ametryn, a triazine herbicide, in sugar cane agriculture and the properties of this herbicide suggest it could be present in the environment as a potential contaminant of soil, surface water, groundwater, and river sediment. In order to clarify the mechanism through which ametryn could be toxic, an in vivo study with Wistar rats was conducted using hematological, biochemical, molecular, morphological and genotoxic approaches. For this purpose, two sub-lethal ametryn concentrations (15 mg and 30 mg/kg/day) were administered to 42 rats divided into three groups (n=12) by gavage during 56 days, whereupon blood, liver and bone marrow were collected. The results showed ametryn genotoxic activity by in vivo micronuclei testing. This event probably occurred as consequence of oxidative stress induction demonstrated by GSTM1 transcript levels increase (indicating complexation between ametryn and/or metabolites with GSH) and by SOD activity decrease. Also, Mn-SOD transcripts were increased, probably avoiding mtDNA damage caused by EROS. These mechanisms displayed hepatic stellate cell (HSCs) activation because two major biomarkers were regulated, connexin and cadherin. N-cad transcripts were increased on both exposed groups while E-cad decreased in the T1 group, indicating epithelial-to-mesenchymal transition. In addition, Cx43 transcripts were decreased suggesting an increase in collagen content. Volumetric proportion of sinusoids was significantly decreased in T1 group and no significant alteration in hepatocyte volume was observed, indicating an increase in the space of Disse, due to fibrosis. Hepatocyte nuclei showed significant decrease in diameter and volume. Few hematological alterations were found. We emphasize the importance of other approaches, such as cell death and proliferation assays, so that ametryn toxicity can better be understood.


Subject(s)
Blood/drug effects , Bone Marrow/drug effects , Herbicides/toxicity , Liver/drug effects , Triazines/toxicity , Animals , Male , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction
2.
Food Chem Toxicol ; 50(11): 3956-62, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22951362

ABSTRACT

Basal generation of reactive oxygen species (ROS) is essential for male reproductive function, whereas high ROS levels may be linked to low quality of sperm and male infertility. The number of antioxidants known to inflict damage is growing, and it will be of interest to study natural products, which may have this activity. Since the epididymis is known to play an important role in providing the microenvironment for sperm maturation and storage of sperm, this study was undertaken to evaluate the morphometric-stereological and functional alterations in the epididymis after chronic treatment with low doses of Brazilian green propolis, which is known for its antioxidant properties. For this purpose, forty-eight adult male Wistar rats were treated with 3, 6 and 10 mg/kg/day of aqueous extract of Brazilian green propolis during 56 days and morphological parameters, sperm production and number of sperm in rat epididymis and oxidative stress levels were analyzed. The results showed higher sperm production and greater epithelium height of the epididymis initial segment and no induction of oxidative stress in treated animals. Further studies are needed to fully understand the effects of propolis on the reproductive system but our results showed that it could alter male reproductive function.


Subject(s)
Epididymis/drug effects , Oxidative Stress/drug effects , Propolis/pharmacology , Animals , Brazil , Catalase/metabolism , Epididymis/anatomy & histology , Male , Microscopy, Electron, Transmission , Organ Size/drug effects , Rats , Rats, Wistar , Sperm Count , Spermatogenesis/drug effects , Thiobarbituric Acid Reactive Substances/metabolism
3.
Ecotoxicol Environ Saf ; 78: 170-7, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22153302

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.


Subject(s)
Atrazine/toxicity , Herbicides/toxicity , Liver/drug effects , Animals , Atrazine/chemistry , Atrazine/metabolism , Body Weight/drug effects , Catalase/metabolism , Cytotoxins/toxicity , Glutathione/metabolism , Glutathione Transferase/metabolism , Herbicides/metabolism , Lipid Peroxidation/drug effects , Liver/metabolism , Liver/pathology , Male , Malondialdehyde/metabolism , Mutagens/toxicity , Oxidative Stress/drug effects , Rats , Rats, Wistar , Superoxide Dismutase/metabolism
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