Carcinogenesis, Teratogenesis & Mutagenesis ›› 2025, Vol. 37 ›› Issue (1): 8-15.doi: 10.3969/j.issn.1004-616x.2025.01.002

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Study on the protective effect of caffeic acid phenethyl ester against sulfur mustard-induced acute lung injury in mice

CAO Meng, WANG Zhen, GAO Tian, YU Weihua, LIU Jiangzheng, KONG Deqin, WU Hao, LONG Zi, WANG Zhao, LIU Rui, HAI Chunxu   

  1. Department of Military Toxicology and Chemical Defense Medicine of the School of Military Preventive Medicine, Air Force Medical University; Key Laboratory of Environmental Hazard Assessment and Prevention of Ministry of Education; Key Laboratory of Environmental Health Hazard Assessment and Protection of Shaanxi Province; Key Laboratory of Free Radical Biology and Medicine of Shaanxi Province, Xi'an 710032, Shaanxi, China
  • Received:2024-10-23 Revised:2024-12-26 Published:2025-01-25

Abstract: OBJECTIVE: To investigate the protective effects and underlying mechanisms of caffeic acid phenethyl ester (CAPE) against acute lung injury induced by exposure to the blister agent 2-chloroethyl ethyl sulfide (CEES) in mice. METHODS: Forty male C57BL/6 mice were exposed to 10% CEES via aerosol inhalation to induce an acute lung injury model. The mice were treated with CAPE (10 mg/kg) at 1,25,and 49 hours post-exposure. Respiratory time (Ti),expiratory time (Te),relaxation time (Tr),and minute ventilation (MVb) were measured on the third day post-exposure as indicators of lung function. Subsequently,the mice were euthanized,and serum and lung tissues were collected to assess body mass and lung-to-body weight ratio. Histopathological examination was performed after hematoxylin and eosin (HE) staining. Reactive oxygen species (ROS) levels in lung tissues were detected using a DHE fluorescent probe. Malondialdehyde (MDA) content,catalase (CAT) activity,and superoxide dismutase (SOD) activity were measured using commercial kits. The mRNA expression levels of antioxidant molecule CAT and inflammatory molecules TNF-α and IL-6 in lung tissues were determined by RT-qPCR. The concentrations of serum inflammatory cytokines TNF-α and IL-6 were measured using ELISA kits. RESULTS: Compared with mice in the CEES-exposed group,mice in the CAPE-treated group exhibited significant recovery in lung function indices,including Ti,Te,Tr,and MVb (all P<0.05),after 3 days of CEES aerosol inhalation. The degree of pathological damage in lung tissues was reduced. Concurrently,the levels of ROS and MDA in the lung tissue were significantly decreased,accompanied by increased levels of CAT and SOD (all P<0.05). Furthermore,the concentrations of TNF-α and IL-6 in both the lung tissue and serum in the CAPE-treated group were significantly lower than those in the CEES-exposed group (all P<0.05). CONCLUSION: CAPE effectively alleviated CEES-induced acute lung injury in mice through its anti-inflammatory and antioxidant properties,suggesting its potential as a therapeutic candidate for vesicant agent poisoning. This study provides a foundation for the investigation of interventional measures and potential therapeutic drugs for the treatment of vesicant agent poisoning.

Key words: blister agent, caffeic acid phenethyl ester, inflammation, oxidative stress, acute lung injury

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