Toxic Exposure to Endocrine Disruptors Worsens Parkinson’s Disease Progression through NRF2/HO-1 Alteration

Abstract

Human exposure to endocrine disruptors (EDs) has attracted considerable attention in recent years. Different studies showed that ED exposure may exacerbate the deterioration of the nervous system’s dopaminergic capacity and cerebral inflammation, suggesting a promotion of neurodegeneration. In that regard, the aim of this research was to investigate the impact of ED exposure on the neuroinflammation and oxidative stress in an experimental model of Parkinson's disease (PD). PD was induced by intraperitoneally injections of MPTP for a total dose of 80 mg/kg for each mouse. Mice were orally exposed to EDs, starting 24 h after the first MPTP administration and continuing through seven additional days. Our results showed that ED exposure raised the loss of TH and DAT induced by the administration of MPTP, as well as increased aggregation of α-synuclein, a key marker of PD. Additionally, oral exposure to EDs induced astrocytes and microglia activation that, in turn, exacerbates oxidative stress, perturbs the Nrf2 signaling pathway and activates the cascade of MAPKs. Finally, we performed behavioral tests to demonstrate that the alterations in the dopaminergic system also reflected behavioral and cognitive alterations. Importantly, these changes are more significant after exposure to atrazine compared to other EDs. The results from our study provide evidence that exposure to EDs may play a role in the development of PD; therefore, exposure to EDs should be limited.

Chronic Exposure to Vinclozolin Induced Fibrosis, Mitochondrial Dysfunction, Oxidative Stress, and Apoptosis in Mice Kidney

“…Additionally, vinclozolin prepubertal exposure in male rats inhibits pubertal maturation and slows the growth of the accessory sex gland and epididymis [ 36 ]. D’Amico and colleagues recently demonstrated that the effect of endocrine disruptor exposure was not limited to the urogenital apparatus [ 23 , 37 ].…”

“…The dose and route of administration were based on previous studies [ 23 , 37 ] and according to a preliminary experiment ( Figure S1 ). Vinclozolin was administered at three doses (30, 100, and 300 mg/kg) for 7 and 14 days.…”

Açai Berry Mitigates Vascular Dementia-Induced Neuropathological Alterations Modulating Nrf-2/Beclin1 Pathways

“…Extracts from cytosol and nucleus were prepared as previously described and incubated with the antibodies anti-NRF-2 (1–500, SCB, Heidelberg, Germany, #sc-365949), anti-heme oxygenase 1 (HO-1; 1-500, SCB, Heidelberg, Germany, #sc-136960), anti-β-tubulin (1–500, SCB, Heidelberg, Germany, #sc-166729), and anti-MAP2 (1–500, SCB, Heidelberg, Germany, #sc-74421) in 1× PBS, 5% w / v non-fat dried milk and 0.1% Tween-20 at 4 °C overnight [ 46 , 47 , 48 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 ]. For the cytosolic and nuclear fraction, blots were also probed with β-actin and lamin A/C protein to ensure that they were filled with equivalent amounts of proteins (1:500; Santa Cruz Biotechnology).…”

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

“…Additionally, they demonstrated an alteration in antioxidant endogenous defense, reflected in an increase in Mn-SOD activity after vinclozolin exposure [ 8 ]. Following this study, D’Amico et al demonstrated that exposure to vinclozolin (and other endocrine disruptors) significantly induced oxidative stress and inflammation, worsening arthritis and Parkinson’s disease in experimental murine models [ 9 , 10 ]. In consideration of the fact that most previous studies investigated the effects of vinclozolin exposure on the reproductive system, we investigated for the first time the impact of long exposure to vinclozolin on the respiratory system [ 11 , 12 ].…”