Chronic Exposure to Endocrine Disruptor Vinclozolin Leads to Lung Damage via Nrf2–Nf-kb Pathway Alterations

Abstract

Endocrine-disrupting substances (EDS) are common and pervasive in our environment and pose a serious risk to both human and animal health. Endocrine-disrupting compounds (EDCs) have been associated with a variety of detrimental human health effects, including respiratory issues, as a result of their ability to disrupt cell physiology. Vinclozolin ((RS)-3-(3,5-Dichlorophenyl)-5-methyl-5-vinyloxazolidine-2,4-dione) is a common dicarboximide fungicide used to treat plant diseases. Several studies have analyzed the effects of vinclozolin exposure on the reproductive system, but less is known about its effect on other organs such as the lung. Mice were exposed for 28 days to orally administered vinclozolin at a dose of 100 mg/kg. Vinclozolin exposure induced histological alterations and collagen depositions in the lung. Additionally, vinclozolin induced inflammation and oxidative stress that led to lung apoptosis. Our study demonstrates for the first time that the toxicological effects of vinclozolin are not limited to the reproductive system but also involve other organs such as the lung.

Effect of Pesticide Vinclozolin Toxicity Exposure on Cardiac Oxidative Stress and Myocardial Damage

“…Most of the studies on VCZ focus mainly on the reproductive system. The VZN toxicity is often associated with increased oxidative stress, for example when ingested in excessive amounts and repeatedly in fish models [ 20 , 21 ]. Previous studies have shown a link between pesticide exposure and cardiotoxicity.…”

“…The toxicity effects from prolonged exposure to VCZ have been well documented. In fact, previous studies have shown how 28-day VCZ exposure can cause histological alteration and fibrosis in several organs such as lung and kidney on mouse [ 20 , 21 ]. The long-term damage caused by VCZ can be even greater, such as damage at behavioral level, affiliative behavior, or motor inhibition in mammals, but also in different class of animals like birds.…”

“…Behind the mechanism of VCZ toxicity appears to be the involvement of oxidative stress, which leads to an imbalance in cellular homeostasis with increased production of markers of inflammation [ 31 ]. For example, in a study on testicular toxicity of VCZ following oral intake, the pesticide was linked to increased oxidative stress with decreased activity of antioxidant enzymes and increased lipid peroxidation in rats [ 20 , 21 ]. These results are in line with studies that relate the toxic action of environmental contaminants to the production of free radicals and increased oxidative stress [ 32 ].…”

Effects of Hyperoxia and Hyperoxic Oscillations on the Proteome of Murine Lung Microvascular Endothelium

“…One example are endocrine disruptors, which are part of plastics (“microplastics”, for example Bisphenol A) or are used as fungicides in agriculture (for example, Vinclozolin). These substances not only have an impact on the reproductive system, but also other organs including the lung by affecting Nrf2/NF-ΚB pathways [ 45 , 46 ].…”

Impact of endocrine disruptors on peripheral blood mononuclear cells in vitro: role of gender

“…Finally, VIN effects on the endocrine system have been reported, evidencing altered male reproduction as the main effect, inducing a lower sperm quality and number, epididymal morpholohical changes, and prostate abnormalities (Anway and Skinner 2008 ; Paoloni-Giacobino 2014 ; Feijó et al 2021 ). Regarding the action on the immune system, only few information are available, namely its ability to interact with NF-κB and with lymphocyte activity, increasing T and B cells percentage, while decreasing NK cells (White et al 2004 ; D’Amico et al 2022b ).…”