Atrazine Inhalation Worsen Pulmonary Fibrosis Regulating the Nuclear Factor-Erythroid 2-Related Factor (Nrf2) Pathways Inducing Brain Comorbidities

Abstract

BACKGROUND/AIMS: Pulmonary fibrosis can be caused by genetic abnormalities, autoimmune disorders or exposure to environmental pollutants. All these causes have in common the excessive production of oxidative stress species that initiate a cascade of molecular mechanism underlying fibrosis in a variety of organs, including lungs. The chemical name of Atrazine (ATR) is 6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine, and it is the most commonly used broad-spectrum herbicide in agricultural crops. Additionally, Bleomycin is a chemotherapeutic agent often used for different lymphoma with a seriously pulmonary complication. The most accredited hypothesis that may explain the mechanism of toxicity induced by ATR or bleomycin is exactly the production of reactive oxygen species (ROS) that leads to an unbalance in the physiological anti-oxidant system. However, until today, nobody has investigated the effect of ATR exposure during pulmonary fibrosis. METHODS: Mice were subject to ATR exposure, to bleomycin injection or to both. At the end of experiment, the lungs and blood were collected. Additionally, we analyzed by different test such as open field, pole and rotarod test or other we investigated the effects of ATR or bleomycin exposure on behavior. RESULTS: Following ATR or bleomycin induction, we found a significant increase in lung damage, fibrosis, and oxidative stress. This condition was significantly worsened when the animals injected with bleomycin were also exposed to ATR. Additionally, we observed significant motor and non-motor impairment in animals exposed to ATR. CONCLUSION: Our study demonstrates that ATR exposure, decrease nuclear factor-erythroid 2-related factor (Nrf2) pathways in both lung and brain.

Antioxidant Activity of a Sicilian Almond Skin Extract Using In Vitro and In Vivo Models

“…The cytosolic and nuclear fractions of the paw tissue were prepared for Western blot analysis as previously described [99]. In order to standardize this procedure, the membranes were treated with anti-NF-κB (1:100) [100], anti-IkB-α (1:100), anti-Nrf2 (1:100), anti-HO-1 (1:100), β-actin (1:500), and β-laminin (1:500) (all purchased from Santa Cruz Biotechnology, Heidelberg, Germany) [101][102][103]. Using BIORAD ChemiDocTM XRS+ software (Version 6.1.0 build 7) and the enhanced chemiluminescence (ECL) detection system reagent, signals were detected, and the relative expression of the protein bands was quantified (Bio-Rad, Milan, Italy) [104].…”

The Role of Nrf2 in Pulmonary Fibrosis: Molecular Mechanisms and Treatment Approaches

“…Oxidative stress stimulates an imbalance between oxidants/antioxidants, which significantly contributes to lung fibrosis [ 108 ]. Exogenous (air pollution, cigarette smoke, silica particles) and endogenous oxidants (mitochondrial ROS, hydrogen peroxide, superoxide anions, and NO) attack alveolar epithelial cells, pulmonary vascular endothelial cells and lung macrophages and induce the formation of ROS and reactive nitrogen species (RNS) [ 10 , 12 , 61 , 109 ]. ROS are important oxidative stress markers, and oxidative stress usually arises from the overproduction of ROS.…”

“…It is characterized by aberrantly activated lung epithelial cells, inflammatory infiltrate, activation of lung fibroblasts, and excessive accumulation of extracellular matrix (ECM) in lung tissues that ultimately lead to respiratory failure, and eventually death if left untreated [ 7 , 8 ]. An array of triggers, including environmental pollutants, herbicides, drug side effects, particles, genetic abnormalities, autoimmune disorders, chronic infection, and cigarette smoking may cause IPF [ 9 , 10 , 11 , 12 ]. Nearly 200,000 people in the United States and over 5 million people worldwide are affected by IPF, and approximately 82–83% of deaths, incident cases, and prevalent cases occur in patients over 70 years old, imposing a great economic burden on the country as well as individuals [ 13 , 14 , 15 ].…”

Toxic Effects of Endocrine Disruptor Exposure on Collagen-Induced Arthritis

“…EDs have gained interest in human physiopathology, as they may interfere with the synthesis, secretion, transport, metabolism, receptor binding, or elimination of endogenous hormones, altering the endocrine and homeostatic systems [2,3]. Indeed, epigenetic changes, such as DNA methylation and/or acetylation and histone modifications, appear to be involved in mechanisms related to endocrine disruption [4][5][6]. The choice of focused categories herein presented is relative to the vast diversity of EDs.…”