Protection by antioxidants against toxicity and apoptosis induced by the sulphur mustard analog 2‐chloroethylethyl sulphide (CEES) in Jurkat T cells and normal human lymphocytes

Han, Suhua; Espinoza, Luis; Liao, Hongling; Boulares, A. Hamid; Smulson, Mark E.

doi:10.1038/sj.bjp.0705591

Cited by 63 publications

(42 citation statements)

References 34 publications

(34 reference statements)

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“…In the present study, we showed that GSPE treatment significantly reduced the cleavage of caspase-3 induced by histones stimulation which is consistent with the anti-apoptotic effect of GSPE previously observed in the perfluorooctanoic acid-induced hepatotoxicity model (Liu et al, 2016). In addition, several other natural antioxidants, such as Bauhinia championii flavone, cyanidin-3-glucoside, and N -acetyl cysteine (NAC) have been previously reported to exert anti-apoptotic effects in cardiomyocytes (Jian et al, 2016), neurons (Ke et al, 2011), and human lymphocytes (Han et al, 2004), respectively.…”

Section: Discussionmentioning

confidence: 99%

Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosis

Chang

Cauvi

et al. 2017

PeerJ

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Apoptosis of lymphocytes is associated with immunosuppression and poor prognosis in sepsis. Our previous report showed that histones, nuclear proteins released from damaged or dying cells in sepsis, can mediate lymphocyte apoptosis via mitochondria damage. Grape seed proanthocyanidin extract (GSPE), a natural substance with protective properties against oxidative stress, plays a vital role in cell and mitochondria protection. We thus hypothesized that GSPE may play a protective role in histone-induced lymphocyte apoptosis through its anti-oxidative properties. In this study, we investigated the protective efficacy of GSPE on lymphocyte apoptosis induced by extracellular histones, a main contributor of death in sepsis. Human blood lymphocytes were treated with 50 μg/ml histones, 2 μg/ml GSPE, or a combination of both. A total of 100 μM N-acetylcysteine (NAC), a reactive oxygen species (ROS) inhibitor, was used as a positive control for GSPE. Apoptosis, intracellular ROS levels, mitochondrial membrane potential, Bcl-2 expression, and caspase-3 cleavage were measured. Our data clearly indicate that GSPE significantly inhibited lymphocyte apoptosis, generation of ROS, the loss of mitochondrial membrane potential, the decrease in Bcl-2 expression, and caspase-3 activation induced by extracellular histones. In conclusion, we show that GSPE has a protective effect on lymphocyte apoptosis induced by extracellular histones. This study suggests GSPE as a potential therapeutic agent that could help reduce lymphocyte apoptosis, and thus the state of immunosuppression was observed in septic patients.

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Section: Discussionmentioning

confidence: 99%

Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosis

Chang

Cauvi

et al. 2017

PeerJ

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“…With similar toxic effects to SM, CEES is a useful SM surrogate used to generate injury models and identify treatment agents [15, 24, 28]. However, it is a monofunctional alkylating agent and a less toxic analog of SM that forms adducts instead of cross-links with cellular molecules [10].…”

Section: Discussionmentioning

confidence: 99%

“…The monofunctional analog of SM, 2-chloroethyl ethyl sulfide (CEES), is extensively used to examine the toxic effects of SM including its DNA damaging properties [15-18]. Like SM, the DNA damage produced by CEES is also reported to be due to its direct alkylating effects, and increased ROS production, that leads to comparable toxic lesions from both these agents [10, 15].…”

Section: Introductionmentioning

confidence: 99%

“…Like SM, the DNA damage produced by CEES is also reported to be due to its direct alkylating effects, and increased ROS production, that leads to comparable toxic lesions from both these agents [10, 15]. Use of antioxidants or inhibitors of ROS formation in both SM and CEES animal models of skin injury have further indicated the role of oxidative stress in vesicant-induced skin injury [3, 12, 19, 20].…”

Section: Introductionmentioning

confidence: 99%

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Catalytic antioxidant AEOL 10150 treatment ameliorates sulfur mustard analog 2-chloroethyl ethyl sulfide-associated cutaneous toxic effects

Tewari‐Singh

Inturi

Jain

et al. 2014

Free Radical Biology and Medicine

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Our previous studies and other published reports with the chemical warfare agent sulfur mustard (SM) and its analog 2-chloroethyl ethyl sulfide (CEES) have indicated a role of oxidative stress in skin injuries caused by these vesicating agents. We examined the effects of the catalytic antioxidant AEOL 10150 in attenuation of CEES-induced toxicity in our established skin injury models (skin epidermal cells and SKH-1 hairless mice) to validate the role of oxidative stress in the pathophysiology of mustard vesicating agents. Treatment of mouse epidermal JB6 and human HaCaT cells with AEOL 10150 (50 μM) 1 h post CEES exposure resulted in significant (p<0.05) reversal of CEES-induced decreases in both cell viability and DNA synthesis. Similarly, AEOL 10150 treatment 1 h after CEES exposure attenuated CEES-induced DNA damage in these cells. Similar AEOL 10150 treatments also caused significant (p<0.05) reversal of CEES-induced decreases in cell viability in normal human epidermal keratinocytes. Cytoplasmic and mitochondrial reactive oxygen species measurements showed that AEOL 10150 treatment drastically ameliorated the CEES-induced oxidative stress in both JB6 and HaCaT cells. Based on AEOL 10150 pharmacokinetic studies in SKH-1 mouse skin, mice were treated with topical formulation plus subcutaneous (injection; 5 mg/kg) AEOL 10150, 1 h after CEES (4 mg/mouse) exposure and every 4 h thereafter for 12 h. This AEOL 10150 treatment regimen resulted in over 50% (p<0.05) reversal in CEES-induced skin bi-fold and epidermal thickness, myeloperoxidase activity, and DNA oxidation in mouse skin. Results from this study demonstrate potential therapeutic efficacy of AEOL 10150 against CEES-mediated cutaneous lesions supporting AEOL 10150 as a medical countermeasure against SM-induced skin injuries.

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“…Depletion of intracellular stores of GSH plays an important role in protecting against oxidative stress by reacting directly with ROS [37][38][39] and NO. 40) Moreover, pretreatment with HT significantly restores the GSH level reduced by t-BHP treatment in HepG2 cells.…”

Section: )mentioning

confidence: 99%

Suppressive Effects of Hydroxytyrosol on Oxidative Stress and Nuclear Factor-κB Activation in THP-1 Cells

Zhang

Cao

Jiang

et al. 2009

Biological & Pharmaceutical Bulletin

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Recent publications have shown that an oxidized cytosolic environment amplifies activation of nuclear factor kappaB (NF-kB), which plays a critical role during inflammatory processes by activating many genes encoding for proinflammatory cytokines and immunoregulatory mediators.1) Some publications have also suggested that reactive oxygen species (ROS) influence inflammatory processes through mechanisms that are dependent on NF-kB.2) In the course of many inflammatory diseases reduced levels of glutathione (GSH) and/or increased levels of free radicals have been detected, 3,4) indicating the involvement of oxidative stress.Hydroxytyrosol (HT), present in the phenolic fraction of virgin olive oil in a concentration range of 10-300 ppm, is abundant in naturally fermented table olives and can be also recovered from virgin olive oil by-products. 5) At nutritionally relevant concentrations, HT possesses marked antioxidant activity and is a good radical scavenger.6,7) HT in vitro prevents protein damage in melanoma cells by ROS induced by long-wave ultraviolet light 8) and DNA damage in Jurkat cells exposed to hydrogen peroxide (H 2 O 2 ).9) Preincubation of intestinal Caco-2 cells with HT prevents the typical damages of oxidative stress. 10) Similarly, HT exerts protective effects against H 2 O 2 -induced oxidative hemolysis and malondialdehyde (MDA) formation in red blood cells.11) It also exerts inhibitory effects on GSH depletion induced by tert-butylhydroperoxide (t-BHP) in HepG2 cells.12) However, little information is available about the effects of HT on oxidative stress and NF-kB activation in LPS-stimulated THP-1 cells. In this study we assessed supression by HT of nitric oxide (NO), ROS, NF-kB activation, and the increase of GSH contents in lipopolysaccharide (LPS)-stimulated THP-1 cells. MATERIALS AND METHODS ChemicalsThe sample of HT was supplied by Eisai Food & Chemical Co., Ltd., Japan. LPS (Escherichia coli LPS, serotype 0127:B8), and 2Ј,7Ј-dichlorofluorescein diacetate (DCFH-DA) were purchased from Sigma (St. Louis, MO, U.S.A.).Cell Culture and Treatment Human monocytic THP-1 cells (American Type Culture Collection, Manassas, VA, U.S.A.) were obtained from Peking Union Medical College (Peking, China) and cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum (Gibco), penicillin (100 U/ml; Gibco), and streptomycin (100 mg/ml; Gibco) at 37°C in a 5% CO 2 -humidified incubator. The cells were treated with or without the indicated concentrations of HT (25, 50, 100 mM) or N-acetylcysteine (NAC) (2.5 mM) for 10 min then incubated with LPS (1.0 mg/ml) for 3 h.Measurement of ROS Intracellular ROS production was measured using DCFH-DA by the method of Bass and coworkers, 13) with some modification. DCFH-DA penetrates the cells and is hydrolyzed by intracellular esterases to the nonfluorescent DCFH, which can be rapidly oxidized to the highly fluorescent 2,7-dichlorofluorescein (DCF) in the presence of ROS. THP-1 monocytes were inoculated into sixwell plates; the numbers of cells were 2ϫ10 5 cells/...

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Protection by antioxidants against toxicity and apoptosis induced by the sulphur mustard analog 2‐chloroethylethyl sulphide (CEES) in Jurkat T cells and normal human lymphocytes

Cited by 63 publications

References 34 publications

Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosis

Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosis

Catalytic antioxidant AEOL 10150 treatment ameliorates sulfur mustard analog 2-chloroethyl ethyl sulfide-associated cutaneous toxic effects

Suppressive Effects of Hydroxytyrosol on Oxidative Stress and Nuclear Factor-κB Activation in THP-1 Cells

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Protection by antioxidants against toxicity and apoptosis induced by the sulphur mustard analog 2‐chloroethylethyl sulphide (CEES) in Jurkat T cells and normal human lymphocytes

Cited by 63 publications

References 34 publications

Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosis

Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosis

Catalytic antioxidant AEOL 10150 treatment ameliorates sulfur mustard analog 2-chloroethyl ethyl sulfide-associated cutaneous toxic effects

Suppressive Effects of Hydroxytyrosol on Oxidative Stress and Nuclear Factor-&kappa;B Activation in THP-1 Cells

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Suppressive Effects of Hydroxytyrosol on Oxidative Stress and Nuclear Factor-κB Activation in THP-1 Cells