Elevated pulmonary levels of Axin2 in mice exposed to herbicide 2,4‐D with or without endotoxin

• Published in: Journal of biochemical and molecular toxicology 2021-12, Vol.35 (12), p.e22912-n/a
• Main Authors: Kaur, Gurvinder, Verma, Ramneek, Mukhopadhyay, Chandra Shekhar, Sethi, Ramsaran
• Format: Article
• Language: English
• Subjects: 2,4-Dichlorophenoxyacetic Acid - administration & dosage; 2,4-Dichlorophenoxyacetic Acid - toxicity; 2,4‐D; Agrochemicals; Animals; Axin Protein - blood; Axin Protein - metabolism; Axin2; Chronic exposure; Dichlorophenoxyacetic acid; DNA microarrays; Down-Regulation - drug effects; endotoxin; Endotoxins; Endotoxins - administration & dosage; Endotoxins - toxicity; Enzyme-linked immunosorbent assay; Exposure; Gene expression; Gene Expression Profiling; Herbicides; Herbicides - administration & dosage; Herbicides - toxicity; Immunohistochemistry; Lipopolysaccharides; Lung - drug effects; Lung - metabolism; Lungs; Male; Mice; Molecular modelling; Oligonucleotide Array Sequence Analysis; Polymerase chain reaction; Signal transduction; Signaling; Toxicity; Transcriptomes; Up-Regulation - drug effects; Wnt protein; Wnt Signaling Pathway - drug effects
• ISSN: 1095-6670; 1099-0461
• DOI: 10.1002/jbt.22912

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.