催化性抗氧化剂AEOL-10150对氮芥诱导小鼠急性肝损伤的保护作用

doi:10.3969/j.issn.1004-616x.2022.01.008

Abstract

Abstract: OBJECTIVE: To investigate protective effects of a catalytic antioxidant AEOL-10150 against nitrogen mustard-induced liver injury and related mechanisms. METHODS: A single intraperitoneal injection of nitrogen mustard hydrochloride (2 mg/kg) was used to construct a nitrogen mustard-induced acute liver injury model in C57BL/6 mice. AEOL-10150 (5 mg/kg) was given 0.5 and 6 h for treatment intervention after nitrogen mustard exposure,and sacrificed after 3 days of exposure. For clarifying the AEOL-10150 has a protective effect on nitrogen mustard-induced liver injury in mice,the following indicators were evaluated:gross liver tissue changes and pathological changes by HE stain;serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities;liver tissue reactive oxygen species (ROS) level,malondialdehyde (MDA) content;reduced glutathione (GSH) content;liver tissue redox regulatory molecule Nrf-2 mRNA and protein expression level;liver tissue myeloperoxidase (MPO) activity,and serum inflammatory factors TNF-α,IL-1β content. RESULTS: A single intraperitoneal exposure of 2 mg/kg nitrogen mustard successfully induced oxidative damage and inflammatory response in livers of mice in the 3rd day. Compared with nitrogen mustard-exposed mice,the AEOL-10150 intervention reduced liver tissue pathological damage,decreased serum ALT and AST activities,and significantly reduced liver tissue ROS and MDA levels,accompanied by the increased GSH content and the decreased Nrf-2 level. In addition,the liver tissue MPO activities and serum TNF-α and IL-1β concentrations of mice in the AEOL-10150 intervention group were significantly lower than those in the nitrogen mustard-exposed group. CONCLUSION: AEOL-10150 effectively alleviated the acute liver injuries which were induced by nitrogen mustard in mice,and its mechanism might be related to direct antioxidant effect and anti-inflammatory effect.

Key words: AEOL-10150, nitrogen mustard, oxidative stress, inflammation, protective effect

CLC Number:

R827.15

AI Duo, XU Anqi, KONG Deqin, LIU Ying, YU Weihua, WANG Zhao, PENG Jie, LIU Rui, ZHANG Xiaodi, HAI Chunxu, LI Wenli, WANG Xin, LIU Jiangzheng. Protective effects of catalytic antioxidant AEOL-10150 against nitrogen mustard-induced acute liver injury in mice[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(1): 40-46,61.

References

[1] 崔海峰. 芥子气中毒事故现场的救治[J]. 沈阳部队医药, 2012(1):77-78.
[2] 董训虎, 陈明亮, 余文珮, 等. 维生素D3通过抑制NLRP3炎性小体激活改善氮芥诱导角质形成细胞炎性损伤[J]. 第三军医大学学报, 2020, 42(3):267-272.
[3] 邹仲敏, 赵吉清, 赛燕, 等. 美国糜烂性毒剂损伤和救治研究项目及其进展[J]. 军事医学, 2012, 36(6):460-464.
[4] ZHANG H, CHEN Y, PEI Z, et al. Protective effects of polydatin against sulfur mustard-induced hepatic injury[J]. Toxicol Appl Pharmacol, 2019, 367:1-11.
[5] 周景艳, 颜新, 左晓丽. 芥子气中毒所致肝功能损害临床分析[J]. 解放军医学杂志, 2003, 28(12):1133.
[6] 赛燕, 赵吉清, 但国蓉, 等. 芥子气损伤机制研究进展[J]. 中国公共卫生, 2011, 27(4):496-499.
[7] BEIGI HARCHEGANI A, KHOR A, TAHMASBPOUR E, et al. Role of oxidative stress and antioxidant therapy in acute and chronic phases of sulfur mustard injuries:a review[J]. Cutan Ocular Toxicol, 2019, 38(1):9-17.
[8] MCELROY C S, MIN E, HUANG J, et al. From the cover:catalytic antioxidant rescue of inhaled sulfur mustard toxicity[J]. Toxicol Sci, 2016, 154(2):341-353.
[9] GAROFALO M C, WARD A A, FARESE A M, et al. A pilot study in rhesus macaques to assess the treatment efficacy of a small molecular weight catalytic metalloporphyrin antioxidant (AEOL 10150) in mitigating radiation-induced lung damage[J]. Health Phys, 2014, 106(1):73-83.
[10] O'NEILL H C, WHITE C W, VERESS L A, et al. Treatment with the catalytic metalloporphyrin AEOL 10150 reduces inflammation and oxidative stress due to inhalation of the sulfur mustard analog 2-chloroethyl ethyl sulfide[J]. Free Radic Biol Med, 2010, 48(9):1188-1196.
[11] BARTOSZ G. Reactive oxygen species:destroyers or messengers?[J]. Biochem Pharmacol, 2009, 77(8):1303-1315.
[12] ZHANG X R, ZHOU W X, ZHANG Y X. Improvements in SOD mimic AEOL-10150, a potent broad-spectrum antioxidant[J]. Mil Med Res, 2018, 5(1):30.
[13] REITMAN S, FRANKEL S. A calorimetric method for the determination of serum glutamate[J]. Am J Clin Pathol, 1957(28):56-63.
[14] ZHANG H, CHEN Y, PEI Z, et al. Protective effects of polydatin against sulfur mustard-induced hepatic injury[J]. Toxicol Appl Pharmacol, 2019, 367:1-11.
[15] 奉水东, 李华文, 王小利, 等. 氮芥所致DNA损伤分子标志物探讨[J]. 中国公共卫生, 2005, 21(2):149-151.
[16] 曾惠, 刘勇, 朱明学, 等. 还原型谷胱甘肽对抗硫芥诱导大鼠脾淋巴细胞毒性作用[J]. 第三军医大学学报, 2006, 28(1):63-65.
[17] MAHER J, YAMAMOTO M. The rise of antioxidant signaling-The evolution and hormetic actions of Nrf2[J]. Toxicol Appl Pharmacol, 2010, 244(1):4-15.
[18] 于丹, 钟玉绪, 李源, 等. 等毒性剂量芥子气诱导大鼠肺损伤炎性因子和蛋白表达变化[J]. 实用医学杂志, 2018, 34(9):1450-1454.
[19] MALAVIYA R, SUNIL V R, VENOSA A, et al. Attenuation of nitrogen mustard-induced pulmonary injury and fibrosis by anti-tumor necrosis factor-α antibody[J]. Toxicol Sci, 2015, 148(1):71-88.
[20] 杨积顺, 徐立平, 胡晋红. 芥子气诱导真皮成纤维细胞分泌肿瘤坏死因子相关凋亡诱导配体的时效和量效研究[J]. 中国药业, 2012, 21(6):29-30.

Protective effects of catalytic antioxidant AEOL-10150 against nitrogen mustard-induced acute liver injury in mice

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	LI Hongwei, KONG Deqin, YU Weihua, WU Hao, WANG Zhao, LIU Rui, HAI Chunxu, WANG Xin, LIU Jiangzheng, LI Wenli. Protective effect of oleanolic acid co-treatment on alcohol-induced oxidative damage in gastric mucosa of rats [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(5): 365-369.
[2]	JIANG Shan, DU Feng, KANG Bingwen, YIN Caocao, ZHOU Jian, SHI Ying, WANG Yue, ZHOU Gengyao, QIN Xujun. Attenuation of D-galactose-induced senescence of human umbilical vein endothelial cells by isorhamnetin [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(2): 95-100.
[3]	ZHAO Junwei, HUA Chenfeng, SHANG Pingping, XIE Fuwei, LI Xiang. Induction of oxidative stress by arsenious acid As(Ⅲ) in A549 cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(1): 28-31.
[4]	LI Dan, LIU Baoying, YU Mingming, ZHUANG Hailin, JIE Jinhua, WU Hanmei. NFKBIA polymorphism, eating habits and susceptibility to gastric cancer: a case-control study [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(3): 198-202.
[5]	SUN Jiaojiao, CHE Bizhong, LUO Qiulin, ZHAI Bingzhong, XIN Lili. 1,25-(OH)₂D₃ attenuates PM_2.5-induced oxidative stress in HBE cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(2): 92-97.
[6]	CHEN Zizhuo, XU Yuhang, ZHAO Jiuzhou, ZHU Jingpu, ZHENG Yipeng, LI Wenli, WU Haozhi, HAI Chunxu, YU Weihua. Antioxidant and anti-inflammatory effects of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside in macrophages [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(2): 105-111,117.
[7]	JIN Lei, ZHOU Jiayou, HAN Jiacheng, GUAN Haojun, WANG Shuai, PENG Jie, WANG Xin, HAI Chunxu, LI Wenli. Protective effects of Jiangzhitong on palmitic acid-induced insulin resistance in BRL-3A cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(1): 21-28.
[8]	LI Yuwen, LI Chen, FENG Jiangbin, FAN Li, LIU Jianxiang, LIU Qingjie, TIAN Mei. Effect of UVB irradiation on TGF-β1,and expression of miRNA and cyclooxygenase-2 in human keratinocytes [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(5): 341-346.
[9]	ZHANG Xuguang, DU Ruihu, CHEN Yanping, ZHAO Yan. Effect from activation of acid sphingomyelinase and ceramide on vitamin E succinate-induced apoptosis in human gastric cancer cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(5): 379-384.
[10]	LIAO Nai, LONG Zi, HAI Chunxu, WANG Xin. 2,3,7,8-tetrachlorodibenzo-p-dioxin alone or in combination with high fat diet on glucose and lipid metabolism in mice [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(2): 111-118.
[11]	WEI Fenfen, WANG Wenjuan, ZHANG Bo. Protective effects of lycium barbarum polysaccharide on kidney in alcohol-induced liver injury in mice [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(2): 148-152.
[12]	LIU Jing, ZHANG Xiaoqiang, WANG Xu, MIAO Xinyu, LU Xiaoxing. Titanium dioxide nanoparticles on expression of inflammatory factors and phosphorylation of JAK2/STAT3 in IEC-6 cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(2): 127-132.
[13]	GUO Haidong, YANG Runfang, LIU Xinyu, LIU Junjun, HE Jin, GAN Ziqiong, LI Hongxia. Oxidative stress response in rats after exposure to fire-drill prop smoke [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(1): 41-44,48.
[14]	WEN Hairuo, GUO Yajuan, HUANG Zhiying, WANG Xue, DAN Mo. Induction of cytotoxicity and DNA damage by iron oxide nanoparticles with different surface modifications in A549 cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2018, 30(6): 413-421.
[15]	ZHOU Xiaoqing, WEN Kexin, YIN Hongping, YANG Jinru, ZHU Yongfei. Effects of intrauterine flutamide exposure on uterus and ovary development and on oxidative stress among female offspring [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2018, 30(5): 384-388,394.