Induction of neuronal damage in guinea pig brain by intratracheal infusion of 2‐chloroethyl ethyl sulfide, a mustard gas analog

Abstract

Intratracheal infusion of 2-chloroethyl ethyl sulfide (CEES), a mustard gas analog and a chemical warfare agent is known to cause massive damage to lung. The purpose of this study was to determine whether intratracheal CEES infusion causes neuronal damage. Histological, immunohistochemical, and Western blot studies indicated that CEES treatment caused dose-dependent increases in blood cell aggregation, microglial cell number, microglial activation, and brain inflammation. In addition, an increased expression of α-synuclein and a decreased expression of the dopamine transporter were observed. The results indicate that intratracheal CEES infusion is associated with changes in brain morphology mediated by an increase in α-synuclein expression, leading to neurotoxicity in a guinea pig model. These changes may be mediated by oxidative stress. Furthermore, the present study indicates for the first time that intratracheal infusion of a single dose of CEES can cause neuroinflammation, which may lead to neurological disorders in later part of life.

Life-Cycle-Dependent Toxicities of Mono- and Bifunctional Alkylating Agents in the 3R-Compliant Model Organism C. elegans

“…The antioxidant response was impaired in the brains of rats exposed to SM [61], and multiple stress markers were observed in the brains of hairless mice after CEES topical exposure [62]. Moreover, intratracheal CEES infusion to guinea pigs resulted in neuroinflammation, α-synuclein accumulation, and decreased DA transporter expression [63], which is in line with our observations. Further studies are needed to link the reduced DAT-1 expression with the other neurotoxic and neurological changes observed upon mustard exposure.…”

Evidence for the systemic diffusion of (2-chloroethyl)-ethyl-sulfide, a sulfur mustard analog, and its deleterious effects in brain

“…Because handling of SM is strictly regulated and banned from most toxicology laboratories by the Organization for the Prohibition of Chemical Weapons (OPCW), other experimental works involved the analog 2-chloroethyl ethyl sulfide (CEES). Neurological effects of CEES confirmed those found for SM in vivo (Gadsden-Gray et al, 2012;Gros-Desormeaux et al, 2018;Sharma et al, 2009). One specific feature of SM and CEES is their ability to induce neuropathological disorders and brain damage after dermal exposure on small skin areas.…”

Possible regulation of the immune modulator tetraspanin CD81 by alpha-synuclein in melanoma

“…It has been shown that α-syn promotes inflammation and immune response in a mouse model of PD [45] and in the peritoneum [46]. We have recently reported that the SK-MEL-28 SNCA -KO clones secrete significantly more IL-1β and more IGFBP5 (Insulin growth factor binding protein 5) than the parental SK-MEL-28 cells [47], which implies that α-syn inhibits the secretion of these factors and thus has a role in immunomodulation. Future work will include mechanistic studies into how α-syn modulates the cell surface expression of proteins and how α-syn modulates immune cell function in the tumor microenvironment.…”