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J Biochem Mol Toxicol ; 35(12): e22912, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34463001

RESUMO

2,4-Dichlorophenoxyacetic acid (2,4-D), a member of the phenoxy family of herbicides is commonly used in agriculture for controlling broadleaf weeds but its uncontrolled and incoherent use has been linked to incidences of lung toxicity. The present study aimed to understand the molecular mechanisms behind the 2,4-D alone or in combination with endotoxin (lipopolysaccharide [LPS]) induced pulmonary toxicity. Blood and lung samples were collected from Swiss albino mice (n = 48) following chronic exposure to high (37 mg/kg; 1/10th of LD50 ) and low (18.5 mg/kg; 1/20th of LD50 ) doses of 2,4-D alone or in combination with endotoxin (80 µg/animal). Transcriptome analysis revealed Wnt Canonical signaling as one of the top dysregulated pathways in mice lung following exposure to 2,4-D with and without endotoxin (LPS) co-exposure. Global view of differentially expressed genes showed increased messenger RNA expression of Axin2 by 0.26, 2.58, 3.14, 2.59, and 2.97 folds following exposure to LPS, high dose alone or in combination with LPS and low dose alone or in combination with LPS, respectively. The microarray data were validated using quantitative polymerase chain reaction and immunohistochemistry. Furthermore, the plasma concentration of Axin2 was elevated in the high dose group as revealed by Sandwich ELISA. The data taken together suggest a role of Axin2 to activate the Canonical Wnt signaling pathway in 2,4-D and or endotoxin-induced lung damage in mice.


Assuntos
Ácido 2,4-Diclorofenoxiacético/toxicidade , Proteína Axina/metabolismo , Endotoxinas/toxicidade , Herbicidas/toxicidade , Pulmão/efeitos dos fármacos , Ácido 2,4-Diclorofenoxiacético/administração & dosagem , Animais , Proteína Axina/sangue , Regulação para Baixo/efeitos dos fármacos , Endotoxinas/administração & dosagem , Perfilação da Expressão Gênica , Herbicidas/administração & dosagem , Pulmão/metabolismo , Masculino , Camundongos , Análise de Sequência com Séries de Oligonucleotídeos , Regulação para Cima/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos
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