Inflammatory and oxidative stress-related effects associated with neurotoxicity are maintained after exclusively prenatal trichloroethylene exposure

Abstract

Trichloroethylene (TCE) is a widespread environmental toxicant with immunotoxic and neurotoxic potential. Previous studies have shown that continuous developmental exposure to TCE encompassing gestation and early life as well as postnatal only exposure in the drinking water of MRL+/+ mice promoted CD4+ T cell immunotoxicity, glutathione depletion and oxidative stress in the cerebellum, as well increased locomotor activity in male offspring. The purpose of this study was to characterize the effects of exclusively prenatal exposure on these parameters. Another goal was to investigate potential plasma oxidative stress/inflammatory biomarkers to possibly be used as predictors of TCE-mediated neurotoxicity. In the current study, 6 week old male offspring of dams exposed gestationally to 0, 0.01, and 0.1 mg/ml TCE in the drinking water were evaluated. Our results confirmed that the oxidized phenotype in plasma and cerebellum was maintained after exclusively prenatal exposure. A Phenotypic analysis by flow cytometry revealed that TCE exposure expanded the effector/memory subset of peripheral CD4+ T cells in association with increased production of pro-inflammatory cytokines IFN-γ and IL-17. Serum biomarkers of oxidative stress and inflammation were also elevated in plasma suggesting that systemic effects are important and may be used to predict neurotoxicity in our model. These results suggested that the prenatal period is a critical stage of life by which the developing CNS and immune system are susceptible to long-lasting changes mediated by TCE.

Curcumin Alleviates Oxaliplatin-Induced Peripheral Neuropathic Pain through Inhibiting Oxidative Stress-Mediated Activation of NF-κB and Mitigating Inflammation

“…The course of treatment and the quality of patients' life have been greatly affected. 22) In recent years, researchers have attached more and more importance to oxidative stress because of its role in the delayed-and accumulated-type of neurotoxicity. 23) Mammalian nerves are known to be more susceptible to oxidative stress because of their high content of phospholipids, mitochondria rich axoplasm and also due to weak cellular antioxidant defence.…”

“…22) In recent years, researchers have attached more and more importance to oxidative stress because of its role in the delayed-and accumulated-type of neurotoxicity. 23) Mammalian nerves are known to be more susceptible to oxidative stress because of their high content of phospholipids, mitochondria rich axoplasm and also due to weak cellular antioxidant defence. 24) In addition, lacking of blood-brain-barrier makes peripheral nervous system more susceptible to the injury of chemotherapeutic accumulation like oxaliplatin, increasing the level of reactive oxygen species (ROS) and destroying the antioxidant-related proteins, and results in the disorder of redox balance in the end.…”

Irreversible effects of trichloroethylene on the gut microbial community and gut‐associated immune responses in autoimmune‐prone mice

“…There is also evidence to suggest that TCE promotes immune-mediated inflammatory diseases, hypersensitivity and autoimmunity in humans (Cooper et al, 2009;Dai et al, 2015;EPA, 2011;Huang et al, 2015;Khader, Gaffen, & Kolls, 2009;Parks & De Roos, 2014;Zhao et al, 2016). We and others have shown the effect of continuous developmental exposure to TCE in mice encompassing gestation, lactation, and early life generated CD4 + T-cell alterations and/or early signs of tissue inflammation in both normal and autoimmune-susceptible mouse strains (Blossom, Melnyk, Li, Wessinger, & Cooney, 2017;Gilbert, Woodruff, & Blossom, 2014;Peden-Adams et al, 2006;Peden-Adams et al, 2008).…”

“…There is also evidence to suggest that TCE promotes immune‐mediated inflammatory diseases, hypersensitivity and autoimmunity in humans (Cooper et al, ; Dai et al, ; EPA, ; Huang et al, ; Khader, Gaffen, & Kolls, ; Parks & De Roos, ; Zhao et al, ). We and others have shown the effect of continuous developmental exposure to TCE in mice encompassing gestation, lactation, and early life generated CD4 + T‐cell alterations and/or early signs of tissue inflammation in both normal and autoimmune‐susceptible mouse strains (Blossom, Melnyk, Li, Wessinger, & Cooney, ; Gilbert, Woodruff, & Blossom, ; Peden‐Adams et al, ; Peden‐Adams et al, ). We recently reported that continuous developmental exposure to TCE beginning at gestation generated autoimmune hepatitis (AIH)‐like tissue pathology at postnatal day (PND) 259 even when TCE was removed from the drinking water at PND154 (Gilbert, Bai, Barnette, & Blossom, ).…”

Epigenetic underpinnings of developmental immunotoxicity and autoimmune disease

“…We and others have shown that continuous developmental exposure to TCE in mice (gestation, lactation, and early life) generated CD4 + Tcell alterations and/or early signs of tissue inflammation in both normal and autoimmune-susceptible mouse strains [58,59]. Similar immune-altering effects were observed with gestation- or postnatal-only exposure in young adult mice [60,61]. We recently reported continuous chronic exposure to low-level TCE beginning at gestation generated autoimmune hepatitis at postnatal day 259 even when TCE exposure was stopped 15 weeks earlier [62].…”