Effects of anti-inflammatory compounds on sulfur mustard injured cells: Recommendations and caveats suggested by in vitro cell culture models

Menacher, Georg; Steinritz, Dirk; Schmidt, Annette; Popp, Tanja; Worek, Franz; Gudermann, Thomas; Thiermann, Horst; Balszuweit, Frank

doi:10.1016/j.toxlet.2017.09.003

Cited by 9 publications

(3 citation statements)

References 37 publications

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“…A dexamethasone (Sigma-Aldrich) stock solution (1 mg/mL in 70% ethanol) was freshly prepared for each experiment. THP-1 cells were treated with final dexamethasone concentrations of 3.2 μM and 6.4 μM according to Menacher et al, 2017 (32).…”

Section: Methodsmentioning

confidence: 99%

Ceylon cinnamon and its major compound Cinnamaldehyde can limit overshooting inflammatory signaling and angiogenesis in vitro: implications for COVID-19 treatment

Lucas

Ackermann

Leifke

et al. 2021

Preprint

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Overshooting immune reactions can occur during inflammatory responses that accompany severe infections, such as COVID-19. Cytokines, damage-associated molecular patterns (DAMPs), and reactive oxygen and nitrogen species can generate positive feedback loops of inflammation, leading to long-term complications such as vascular endothelialitis, thrombosis, endothelial dysfunction, neurological impairments, and chronic fatigue. Dexamethasone can limit inflammation by inhibiting the activation of pro-inflammatory transcription factors. High dose dexamethasone, however, has undesirable side effects. Here, we show that Ceylon cinnamon and its major compound cinnamaldehyde can mitigate inflammatory signaling in vitro. Cinnamaldehyde interferes with the dimerization of toll-like receptor 4 (TLR4), which can be activated by DAMPs like HSP60 and HMGB1. Our results suggest that supplementary treatment with Ceylon cinnamon may allow administration of lower doses of dexamethasone to avoid high dose steroid side effects. Moreover, preliminary results indicate that Ceylon cinnamon modulates angiogenesis, which is a reactive phenomenon in COVID-19.

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Section: Methodsmentioning

confidence: 99%

Ceylon cinnamon and its major compound Cinnamaldehyde can limit overshooting inflammatory signaling and angiogenesis in vitro: implications for COVID-19 treatment

Lucas

Ackermann

Leifke

et al. 2021

Preprint

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show abstract

“…Moreover, during the recent decades, it was applied against some nations such as Iran and Syria, too. [1][2][3] Cellular and molecular biology-based studies have indicated that SM can alkylate DNA and proteins, destroy enzymes, induce free radicals, and finally can cause necrosis and apoptosis in cells. In addition to death and acute complications, SM can cause long-term side effects on the lungs, skin, and eyes of its victims.…”

Section: Introductionmentioning

confidence: 99%

“…However, a variety of antioxidant drugs such as N-acetylcysteine and anti-inflammatory drugs like corticosteroids have been used in this regard although these compounds have not been very effective. 2,3,7 Curcumin [1,7-bis (4-hydroxy-3methoxyphenyl) -1, 6-heptadiene-3, 5-dione] is a lowmolecular-weight, a hydrophobic polyphenolic compound found in the underground stem of Curcuma longa that is generally called turmeric. Curcumin has many health benefits including antioxidant, antimicrobial, anti-inflammatory, anti-viral, and anticancer effects that have been approved by the FDA, FAO, and WHO.…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory Effect of Curcumin in the Upregulation of Inflammasome Pathway Genes Induced by Sulfur Mustard Analog: An In-vitro Study

Chehardoli¹,

Nadi²,

Abadi³

et al. 2021

IJAAI

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Sulfur Mustard (SM) induces cell injury via exerting oxidative stress, protease-anti protease imbalance, and inflammation. Inflammasome as one part of innate immunity has a critical role in the recognition of cell injuries and the initiation of the inflammation process by releasing IL-1β. Hence, the present study investigated the effects of the sub-lethal doses of 2-chloroethyl ethyl sulfide (CEES) as SM analog on the gene expression level of inflammasome-related genes as well as the potential protective effects of curcumin on this process. The effects of sub-lethal doses (500, 1000, and 2500 mM) of CEES on pulmonary epithelial cell line (A549) were determined at various time points (12, 24, and 48 h). Following the treatment of cells with CEES, the kinetic alterations of the expression levels of nuclear factor kappa-light-chainenhancer of activated B cells (NF-ĸB1), NLR family pyrin domain containing 1 (NLRP1), Caspase-1 (Casp1), and Interleukin-1β (IL-1β) genes were analyzed; using real-time PCR. In addition, the concurrent protective effects of different doses of curcumin (20, 40, 80, and 160 mM) on modulating the effects of CEES were studied. Although it was found that the lowest sub-lethal dose of CEES (500 mM) was able to upregulate the inflammasome-related genes, the maximum alterations occurred 48 h after the treatment with the higher sub-lethal dose (2500 mM) of CEES. The maximum alteration occurred in Casp1 (38 fold), IL-1β (19 fold), and NLRP1 (~4 fold) genes (p<0.0001). However, the NF-ĸB gene expression level did not alter following CEES exposure. Even though low doses of curcumin (20, 40, and 80 mM) were able to down-regulate the studied genes, it was found that the treatment of cells with 160 mM of curcumin for 48 h was able to normalize the expression level of all genes. The present study concludes that curcumin as an anti-inflammatory agent may have beneficial immunomodulatory effects following CEES exposure.

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Dermal toxicity of sulfur mustard

Gray¹,

Shakarjian²,

Gerecke³

et al. 2020

Handbook of Toxicology of Chemical Warfare Agents

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Effects of anti-inflammatory compounds on sulfur mustard injured cells: Recommendations and caveats suggested by in vitro cell culture models

Cited by 9 publications

References 37 publications

Ceylon cinnamon and its major compound Cinnamaldehyde can limit overshooting inflammatory signaling and angiogenesis in vitro: implications for COVID-19 treatment

Ceylon cinnamon and its major compound Cinnamaldehyde can limit overshooting inflammatory signaling and angiogenesis in vitro: implications for COVID-19 treatment

Immunomodulatory Effect of Curcumin in the Upregulation of Inflammasome Pathway Genes Induced by Sulfur Mustard Analog: An In-vitro Study

Dermal toxicity of sulfur mustard

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