RESUMO
The aim of the present study was to compare the effect of oral and subcutaneous exposure to a glyphosate-based herbicide (GBH) on the female reproductive system, specifically in the ovaries and uterus of prepubertal lambs. To this end, ewe lambs were exposed to a s.c. (n: 5) or an oral (n: 5) environmentally relevant dose of GBH (2â¯mg/kg/day) or to vehicle (controls, n: 12), from postnatal day (PND) 1 to PND14. Serum glyphosate and aminomethylphosphonic acid (AMPA) concentrations were measured on PND15 and PND45. The ovaries and uterus were obtained and weighed on PND45. Ovarian follicular dynamics and uterine morphological features were determined by picrosirius-hematoxylin staining. The proliferation marker Ki67 was evaluated by immunohistochemistry in ovarian and uterine samples. Glyphosate but not AMPA was detected in serum of exposed lambs on PND15, whereas neither glyphosate nor AMPA were detected on PND45. Controls were negative for glyphosate and AMPA on PND15 and PND45. GBH exposure did not affect ovarian or uterine weight. However, on PND45, the ovary of GBH-exposed lambs showed altered follicular dynamics, increased proliferation of granulosa and theca cells, and decreased mRNA expression of FSHR and GDF9, whereas their uterus showed decreased cell proliferation but no alterations in the histomorphology or gene expression. In conclusion, GBH exposure altered the ovarian follicular dynamics and gene expression, and the proliferative activity of the ovaries and uterus of lambs. It is noteworthy that all the adverse effects found in the ovaries and uterus of both GBH-exposed groups were similar, independently of the administration route.
Assuntos
Glicina/análogos & derivados , Herbicidas/efeitos adversos , Ovário/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Útero/efeitos dos fármacos , Administração Oral , Animais , Animais Recém-Nascidos , Proliferação de Células , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Glicina/efeitos adversos , Glicina/sangue , Glicina/farmacologia , Fator 9 de Diferenciação de Crescimento/genética , Herbicidas/sangue , Herbicidas/farmacologia , Injeções Subcutâneas , Isoxazóis/sangue , Tamanho do Órgão/efeitos dos fármacos , Ovário/citologia , Ovário/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/genética , Receptores do FSH/genética , Carneiro Doméstico , Tetrazóis/sangue , Útero/citologia , Útero/metabolismo , GlifosatoRESUMO
Atrazine is an endocrine disruptor affecting testicular steroidogenesis, and promoting testicular atrophy and 3ß-HSD reduction. However, it remains unknown whether these effects are reversible or permanent. To address this issue was the aim of this study. Exposition of rats to 200mg/kg of atrazine resulted in transient increase in testicular weight, seminiferous tubules dilation and atrophy, and reduction in Leydig cell 3ß-HSD. Testicular atrophy and 3ß-HSD reduction were more pronounced after the recovery period of 75days. There was increase in aromatase expression after long-term exposure but it returned to control level after recovery. Moreover, there was increase in ED1-/ED2+, ED1+/ED2+ and ED1+/ED2- macrophages, in the recovery group. These macrophages were positive for 3ß-HSD, thereby raising possibility of their involvement in steroidogenesis. These findings further emphasize the adverse effects of atrazine on male reproduction, highlighting that testicular damages may be irreversible even after a recovery period longer than the spermatogenic cycle.
Assuntos
Atrazina/toxicidade , Herbicidas/toxicidade , Testículo/efeitos dos fármacos , 3-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Aromatase/metabolismo , Atrazina/sangue , Herbicidas/sangue , Macrófagos/efeitos dos fármacos , Macrófagos/enzimologia , Masculino , Ratos Wistar , Testículo/metabolismo , Testículo/patologiaRESUMO
Introducción. El glifosato es un herbicida de amplio espectro, no selectivo, utilizado comúnmente en agricultura para eliminar malezas. Los estudios que han evaluado la toxicidad del glifosato en animales y en ambiente muestran que las formulaciones comerciales son más tóxicas que el componente activo. Objetivos. Evaluar la toxicidad del glifosato grado técnico y de la formulación comercial Roundup® en células mononucleares de sangre periférica humana. Materiales y métodos. Células mononucleares de sangre periférica humana fueron expuestas a diferentes concentraciones de glifosato en grado técnico y en la forma de Roundup® por 24, 48, 72 y 96 horas. La citotoxicidad se evaluó mediante el método de exclusión con azul de tripano y reducción del reactivo sal sódica de (2,3-bis[2-metoxi-4-nitro-5-sulfofenil]-2Htetrazolio-5-carboxianilida) (XTT). Resultados. Ambas presentaciones del glifosato (grado técnico y Roundup®) fueron tóxicas para las células mononucleares de sangre periférica humana. Roundup® fue más citotóxico que el glifosato grado técnico, ya que se encontró que la concentración letal 50 (LC50) analizada con el método de exclusión con azul de tripano a las 24 horas fue de 56,4 µg/ml de glifosato en la forma de Roundup® y de 1.640 mg/ml (1,64 µg/ml) para glifosato grado técnico. Conclusiones. Los resultados de este estudio in vitro confirman el efecto tóxico para las células humanas observado para el glifosato y sus preparaciones comerciales, y que estas últimas son más citotóxicas que el compuesto activo, lo que apoya la idea de que los aditivos presentes en las formulaciones comerciales juegan un papel crucial en la toxicidad atribuida a los herbicidas que contienen glifosato.
Introduction. Glyphosate is a broad-spectrum, non-selective herbicide and commonly used to eliminate weeds in agricultural and forest settings. Studies evaluating glyphosate toxicity in animals and environment show that commercial formulations of glyphosate are more toxic than the active component itself. Objectives. Technical grade glyphosate was compared with the commercial formulation Roundup® in their respective toxicities on human peripheral blood mononuclear cells. Materials and methods. Human peripheral blood mononuclear cells were exposed to different concentrations of glyphosate, either technical grade or in the form of Roundup for 24 h, 48 h, 72 h, and 96 h. Cytotoxicity was assayed by trypan blue dye exclusion method and reduction of (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2Htetrazolium-5-carboxyanilide inner salt) XTT reagent. Results. Both technical grade glyphosate and Roundup® formulation were toxic to human peripheral blood mononuclear cells. Cytotoxicity of Roundup® was higher than cytotoxicity of glyphosate, since the LC50 (50% lethal concentration) determined by the trypan blue exclusion method at 24 h was the equivalent of 56.4 ìg/ml of glyphosate in the form of Roundup® and 1,640 ìg/ml (1.64 mg/ml) for technical grade glyphosate. Conclusions. This in vitro study confirmed the toxic effects on human cells by glyphosate and its commercial preparations. Commercial formulations were more cytotoxic than the active component alone, supporting the concept that additives in commercial formulations play a role in the toxicity attributed to glyphosate-based herbicides.
Assuntos
Humanos , Testes Imunológicos de Citotoxicidade , Herbicidas/sangue , Herbicidas/toxicidade , Sobrevivência Celular , Sais de Tetrazólio , Azul TripanoRESUMO
In the present work, a method was developed and optimized aiming to determinate the herbicides paraquat (PQ) and diquat (DQ) in human plasma and urine samples. An initial procedure of chemical reduction of the analytes by adding NaBH4 directly in the buffered samples (pH 8.0) was performed. This procedure was necessary to convert the quaternary ammonium substances into more volatile compounds for gas chromatographic analysis. The reduction compounds were extracted with C18 cartridges (solid-phase extraction). Ethyl paraquat (EPQ) was used as internal standard (IS). Gas chromatography-mass spectrometry (GC-MS) was used to identify and quantify the analytes in selected ion monitoring (SIM) mode. The limits of detection were 0.05 mg/l for both PQ and DQ. By using the weighted least squares linear regression (1/x1/2 for plasma and 1/y for urine), the accuracy of the analytical method was improved at the lower end of the calibration curve (from 0.1 to 50 mg/l; r>0.98). This method can be readily utilized as an important tool to confirm the suspicion of PQ and/or DQ poisoning and evaluate the extent of the intoxication.
Assuntos
Diquat/sangue , Diquat/urina , Cromatografia Gasosa-Espectrometria de Massas/métodos , Paraquat/sangue , Paraquat/urina , Diquat/química , Herbicidas/sangue , Herbicidas/química , Herbicidas/urina , Humanos , Estrutura Molecular , Paraquat/química , Reprodutibilidade dos TestesRESUMO
The acute toxicity of 2,4-dichlorophenoxyacetic acid (2,4-D), a herbicide, was studied in chicks dosed with 100, 300, 500, or 600 mg 2,4-D/kg BW, by the oral route. Clinical, laboratory, and histopathological methods were used as indicators of toxicity. After acute exposure, the herbicide decreased motor activity and induced muscular weakness and motor incoordination; decreased weight gain; increased serum creatine kinase (CK) and alkaline phosphatase (AP) activities and serum uric acid (UA), creatinine (CR), and total proteins (TP) levels; and did not change serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) activities. These changes were time- and dose-dependent and reversible. The LD50 (lethal dose 50%) calculated for oral 2,4-D in chicks was 420 mg/kg BW (385 to 483). Chromatographic analysis of the serum of the intoxicated chicks showed the presence of the herbicide; the amount found was dose- and time-dependent, increasing from 2 to 8 h after exposure and decreasing afterwards. Histopathological post-mortem studies conducted on intoxicated chicks showed hepatic (vacuolar degeneration of the hepatocytes), renal (tubular nephrosis), and intestinal (hemorrhagic) lesions. Taken together, the observed alterations mainly reflected kidney and muscle tissue damage, although hepatic toxicity may also have occurred after acute 2,4-D intoxication.
Assuntos
Ácido 2,4-Diclorofenoxiacético/toxicidade , Galinhas/fisiologia , Herbicidas/toxicidade , Aumento de Peso/efeitos dos fármacos , Ácido 2,4-Diclorofenoxiacético/administração & dosagem , Ácido 2,4-Diclorofenoxiacético/sangue , Administração Oral , Alanina Transaminase/sangue , Alanina Transaminase/efeitos dos fármacos , Fosfatase Alcalina/sangue , Fosfatase Alcalina/efeitos dos fármacos , Animais , Aspartato Aminotransferases/sangue , Aspartato Aminotransferases/efeitos dos fármacos , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/efeitos dos fármacos , Galinhas/sangue , Estudos de Coortes , Creatina Quinase/sangue , Creatina Quinase/efeitos dos fármacos , Creatinina/sangue , Relação Dose-Resposta a Droga , Herbicidas/administração & dosagem , Herbicidas/sangue , Dose Letal Mediana , Masculino , Distribuição Aleatória , Fatores de Tempo , Ácido Úrico/sangue , Ácido Úrico/metabolismo , Aumento de Peso/fisiologiaRESUMO
The acute toxicity of 2,4-dichlorophenoxyacetic acid (2,4-D) was studied in cattle. Steers were dosed po with 100, 300 or 600 mg 2,4-D/kg bw. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), O-glutamyl transferase (O-GT), creatine kinase (CK), lactate dehydrogenase (LDH) activities and urea, creatinine, glucose, total proteins and albumin levels were determined at intervals after dosing. The lowest 2,4-D dose did not change the biochemical parameters studied; the 300 mg/kg dose decreased AST, O-GT and CK activities and increased urea and glucose levels; the highest dose of 2,4-D increased LDH and CK activities and protein, urea, creatinine and glucose levels. These changes were time and dose-dependent and completely reversible. Acute 2,4-D intoxication disrupted the serum levels of several enzymes and blood components which mainly reflect kidney and muscle damage induced by the herbicide.