Delayed effects of sulfur mustard on autophagy suppression in chemically-injured lung tissue

• Published in: International immunopharmacology 2020-03, Vol.80, p.105896, Article 105896
• Main Authors: Eghtedardoost, Marzieh, Ghazanfari, Tooba, Sadeghipour, Alireza, Hassan, Zuhair Mohammad, Ghanei, Mostafa, Ghavami, Saeid
• Format: Article
• Language: English
• Subjects: Autophagy; Beclin-1; Cellular stress response; Complications; Exposure; Formalin-fixed paraffin-embedded (FFPE); Gene expression; Hemostasis; Hemostatics; Immunoblotting; Immunohistochemistry; Intracellular; Lung; Lungs; Microtubule-associated protein light chain 3-B (LC3-B); Mustard gas; Oxidative stress; Paraffin; Paraffins; Phagocytosis; Proteins; Salbutamol; Sulfur
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2019.105896

•The Sulfur mustard gas could up regulate LC3 gene expression in lung 30 years after exposure.•The delayed effect of Sulfur mustard gas down regulate LC3 protein in lung of exposed people.•N-acetyl cysteine and salbutamol drugs by induce the autophagy help to reduce the SM delayed effects. Autophagy is an intracellular hemostasis mechanism, responding to extracellular or intracellular stresses. Sulfur mustard (SM) induces cellular stress. Iranian soldiers exposed to SM gas, during the Iraq-Iran war, suffer from delayed complications even 30 years after exposure. In this study, for exploring the SM effect on autophagy pathway, gene and protein expression of autophagy markers are evaluated in the lung of SM-exposed people. 52 FFPE lung tissues of SM-exposed people and 33 lung paraffin blocks of non-exposed patients to SM were selected. LC3 and Beclin-1 mRNA expressions were evaluated by QRT-PCR. LC3-B protein and LC3II/LC3I proteins ratio were detected by Immunohistochemistry and immunoblotting method. The collected data were analyzed in SPSS, and P value ≤ 0.05 was considered significant. LC3 gene expression in SM-exposed subjects (median CT value = 4.97) increased about 4 fold compared with the control group (median CT value = 0.46, P = 0.025). Beclin-1 mRNA expression had not significant difference between two groups. After adjusting the confounding variables such as drug usage, LC3-B protein (P = 0.041) and LC3II/LC3I ratio (P = 0.044) were found significantly lower in the lung cells of SM-exposed group. Upon exposure to SM gas, the lung cells are affected by acute cellular stress such as oxidative stress. The study results show that LC3 mRNA level increases in these patients, but, surprisingly, LC3-B protein via unknown mechanism has been down-regulated. N-acetyl cysteine and salbutamol drugs could induce the autophagy, and help to reduce the SM effects and improve the clinical condition of SM-injured patients.