Alterations in Mitochondrial and Inflammasome Homeostasis by 2-Chloroethyl Ethyl Sulfide and their Mitigation by Curcumin: An In vitro Study

Azam Kia; Mona Nadi; Vahideh Hajhasan; Jafar Salimian

doi:10.18502/ijaai.v20i5.7411

Azam Kia Basic Science School, East branch, Payame Noor University, Tehran, Iran
Mona Nadi Department of Cell and Molecular Biology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
Vahideh Hajhasan Department of Cell and Molecular Biology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
Jafar Salimian Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v20i5.7411

Keywords: 2-chloroethyl ethyl sulfide; Curcumin; Inflammasomes; Mitochondrial genes

Abstract

The mitochondrion has a substantial role in innate immunity and inflammasome signaling pathways. Sulfur mustard (SM) induces toxicity in cytoplasmic organelles. We aimed to evaluate the potential therapeutic effect of curcumin on the toxicity of SM analog through measuring gene expression levels of mitochondrial dynamics followed by induction of the inflammasome signaling pathway.

After the treatment of pulmonary epithelial cell line (A549) by 2-chloroethyl ethyl sulfide (CEES) (2500 mM) for 48h, the transcriptional activity of mitochondrial fission and fusion genes such as dynamin-related protein 1 (Drp1), mitochondrial fission 1 protein (Fis1), mitofusin-1 (Mfn1), mitofusin-2 (Mfn2), and Dominant optic atrophy (Opa1) and inflammasome pathway genes including absent in melanoma 2 (AIM2), NLR family containing protein 3 (NLRP3), and Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) was measured. Furthermore, the inhibitory effect of curcumin (160 mM) concurrent with SM analog on the expression level of mitochondria and inflammasome genes was investigated.

CEES was able to over-express the fission, fusion (Drp1 ~ 8, Fis1 4.5, Mfn2 15, and Opa1 16-fold) and inflammasome genes (AIM2, NLRP3, 8 and 6-fold, respectively), whereas Mfn1 was significantly decreased (0.5-fold) and a not statistically significant decrease was observed in the ASC gene. Curcumin could modulate the effect of CEES, mitigate the expression of fission, fusion, and inflammasome genes exceedingly. However, a major increase in the repairer fusion gene (Mfn1, 6-fold) and complete suppression of the ASC gene were the outcomes of using the curcumin.

In conclusion, we suggest curcumin alleviates the disturbance of mitochondrial dynamics and downregulates the inflammasome genes exposed to the CEES.