Chloroacetic acid triggers apoptosis in neuronal cells via a reactive oxygen species-induced endoplasmic reticulum stress signaling pathway

The Effect of Chronic Intoxication with 2-Chloroethanol on Immune Responses, Function of Th1 and Th2 Lymphocytes and Blood Cytokine Concentrations

“…The mean activity of Th1 cells (AFC to RSBC -IgM, DTH) and Th2 lymphocytes (AOK to RSBC -IgG) [7,8] after chronic intoxication of CE decreased almost the same -respectively, by 46.4 and 42.9%. Suppression of the main parameters of the immunity system is due to the action on them of both the toxicant molecule and its more toxic metabolites formed as a result of the oxidation of CE by alcohol dehydrogenase and aldehyde dehydrogenase, respectively, to chloroacetaldehyde and chloroacetic acid [1][2][3][4][5][6][7][8][9], which inhibit the cycle tricarboxylic acids in mitochondria of lymphocytes and other blood cells [4,5]. The effect of CE (Table 2) led to decrease of concentration in blood of IFN-γ, interleukins IL-2, IL-4, respectively, by 37.9; 40.9; 44.4% (p<0.05), pro-inflammatory cytokines TNF-α, IL-6 -by 36.7 and 33.3% (p<0.05) respectively, anti-inflammatory cytokines IL-10, IL-13, respectively by 30.1 and 28.4% (p<0.05).…”

“…Decrease in blood of IL-2 after intoxication of CE probably indicates the suppression of its production by T cells, including Th0 and Th1 type lymphocytes, reduction of T and B cells proliferation, and NK activity [11]. Reduction in blood of IL-4, apparently, occurs due to defeat of predominantly Th2 lymphocytes [7][8][9][10][11][12] by the toxicant and its metabolism products [3][4][5][6][7][8][9], and reduction of pro-inflammatory cytokine TNF-α and IL-6 characterizes decrease of their synthesis by macrophages, monocytes and lymphoid dendritic cells, as well as (in relation to IL-6)-Th0, Th2 lymphocytes and fibroblasts [7][8][9][10][11][12][13]. Reduction of concentration of anti-inflammatory cytokine IL-10 in blood is due to decrease in its production of Th2-, B lymphocytes, cells of monocyte-macrophage system, and IL-13 by Th2 lymphocytes [7][8][9][10][11][12][13][14][15].…”

“…These changes are mainly due to products of its biotransformation (chloroacetaldehyde and chloroacetic acid) that are more toxic than CE [3][4][5][6][7][8][9]. The main mechanisms for reducing the function of lymphocytes and other cells of the immunity system under influence of CE are apparently inhibition of tricarboxylic acid cycle in mitochondria of immune system cells [5] and initiation of lipid peroxidation of blood cell membranes [4][5][6][7][8].…”

Advanced oxidation protein products induce apoptosis in podocytes through induction of endoplasmic reticulum stress

“…Accumulating evidence suggests that ER stress is tightly linked to oxidative stress [2,6,20]. Furthermore, it has been shown that AOPP-induced ER stress in adipocytes is mediated by the activation of NADPH oxidasedependent ROS generation [43].…”

Adverse Outcome Pathway on binding of agonists to ionotropic glutamate receptors in adult brain leading to excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment

“…ROS are known to stimulate a number of events and pathways that lead to apoptosis, triggered by ROS-induced ER stress signalling pathway (Lu et al, 2014), caspase-dependent and -independent apoptosis (Zhou et al, 2015) and mitogen-activated protein kinase (MAPK) signal transduction pathways (reviewed in Cuadrado and Nebreda, 2010;Harper and LoGrasso, 2001). …”