Effect of S-adenosyl-l-methionine on oxidative stress and alveolar septal cell apoptosis in mice with emphysema after smoking cessation_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

ZHANG Yanmei ¹ ,  ZHANG Cheng ^1,2,3

1. School of Clinical Medicine, Zunyi Medical University, Zunyi, Guizhou 563000, P. R. China;
2. Department of Respiratory and Critical Care Medicine, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, P. R. China;
3. NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China;

Corresponding?author：

ZHANG Cheng, Email: zhangcheng16@sina.com

Keywords：

Emphysema; oxidative stress; S-adenosine methionine; cigarette smoke; alveolar septal cells; apoptosis

DOI：

10.7507/1671-6205.202403063

Video：

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Objective To investigate the effect of S-adenosyl-l-methionine (SAM) on oxidative stress and alveolar septal cell apoptosis in mice with emphysema after smoking cessation. Methods Twenty-two male SPF C57BL/6J mice aged 6 - 8 weeks were randomly divided into 4 groups, ie. a healthy control group, an emphysema group, a smoking cessation group, and a SAM intervention for 8 weeks after smoking cessation group, with 8 mice in each group. The mice model of emphysema was established by intraperitoneal injection of cigarette smoke extract (CSE) combined with cigarette smoke exposure. Smoking cessation started after the emphysema model was successfully constructed and lasted for 8 weeks. After smoking cessation, the mice in SAM intervention groups were intraperitoneally injected with SAM mg·kg^–1·d^–1 for 8 weeks. The right lung sections of the mice were taken for hematoxylin-eosin staining to observe pathological changes, and the mean linea rintercept (MLI) and mean alveola rnumber (MAN) of lungs were measured. The concentrations of malondialdehyde (MDA), superoxide-dismutase (SOD) and glutathione (GSH) in alveolar lavage fluid of left lung were detected by spectrophotometry. Terminal deoxynucleotidyl transferasemediated dUTP nick end labeling (TUNEL) technique was carried out to detect the alveolar septal cells apoptosis. Results MLI, apoptosis index of alveolar septal cell and MDA concentration in bronchoalveolar lavage fluid (BALF) increased significantly in the emphysema group compared with healthy controls, increased significantly in the smoking cessation group compared with the emphysema group, and decreased in the SAM intervention group compared with the smoking cessation group (all P<0.05). GSH concentration and SOD activity in BALF and MAN was significantly lower in the emphysema group compared with the healthy control group, significantly lower in the smoking cessation group compared with the emphysema group, and significantly higher in the SAM intervention group compared with the smoking cessation group (all P<0.05). Conclusions Lung histopathology and apoptosis of alveolar septal cells in emphysema mice progress continuously after smoking cessation. SAM may reduce oxidative stress and improve apoptosis of alveolar septal cells, so as to protect emphysema mice after smoking cessation.

Citation： ZHANG Yanmei, ZHANG Cheng. Effect of S-adenosyl-l-methionine on oxidative stress and alveolar septal cell apoptosis in mice with emphysema after smoking cessation. Chinese Journal of Respiratory and Critical Care Medicine, 2024, 23(11): 797-801. doi: 10.7507/1671-6205.202403063 Copy

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2.	Xia X, Xiang X, Huang F, et al. Dietary canolol induces apoptosis in human cervical carcinoma HeLa cells through ROS-MAPK mediated mitochondrial signaling pathway: in vitro and in vivo. Chem Biol Interact, 2019, 300: 138-150.
3.	Purohit V, Abdelmalek MF, Barve S, et al. Role of S-adenosylmethionine, folate, and betaine in the treatment of alcoholic liver disease: summary of a symposium. Am J Clin Nutr, 2007, 86(1): 14-24.
4.	Ara AI, Xia M, Ramani K, et al. S-adenosylmethionine inhibits lipopolysaccharide -induced gene expression via modulation of histone methylation. Hepatology, 2008, 47(5): 1655-1666.
5.	張野, 張程, 李夏, 等. SAM對大鼠自身免疫性肺氣腫氧化應激的干預. 重慶醫科大學學報, 2020, 45(11): 1528-1531.
6.	He S, Li L, Sun S, et al. A novel murine chronic obstructive pulmonary disease model and the pathogenic role of microRNA-21. Front Physiol, 2018, 9: 503.
7.	張順, 楊福全, 李航宇, 等. S-腺苷甲硫氨酸對大鼠重癥急性胰腺炎的保護作用. 中國現代普通外科進展, 2011, 14(9): 680-683.
8.	Li D, Li BX, Zhang Y, et al. SAM protects against alveolar septal cell apoptosis in autoimmune emphysema rats. Eur J Med Res, 2023, 28(1): 460.
9.	Li N, Dai Z, Wang Z, et al. Gut microbiota dysbiosis contributes to the development of chronic obstructive pulmonary disease. Respir Res, 2021, 22(1): 274.
10.	張靜, 郭一銘, 李恩紅, 等. 甘草甜素對小鼠矽肺纖維化的干預作用. 安徽醫科大學學報, 2022, 57(1): 121-125.
11.	郭欣, 胡代菊, 梅曉冬. 煙霧暴露小鼠肺部氧化應激與炎癥的變化及戒煙的影響. 安徽醫科大學學報, 2015, 50(6): 757-760.
12.	李正歡, 張曉云, 陳楊, 等. 2020年慢性阻塞性肺疾病全球倡議《COPD診斷、治療與預防全球策略》指南解讀(一)穩定期藥物管理. 中國全科醫學, 2021, 24(8): 923-929.
13.	Josephs L, Culliford D, Johnson M, et al. Improved outcomes in ex-smokers with COPD: a UK primary care observational cohort study. Eur Respir J, 2017, 49(5): 1602114.
14.	Yan H, Zhao L, Wu X, et al. Inflammation and pathological damage to the lungs of mice are only partially reversed following smoking cessation on subacute exposure to cigarette smoke. Mol Med Rep, 2015, 11(6): 4246-4254.
15.	De Cunto G, Bartalesi B, Cavarra E, et al. Ongoing lung inflammation and disease progression in mice after smoking cessation: beneficial effects of formyl-peptide receptor blockade. Am J Pathol, 2018, 188(10): 2195-2206.
16.	Brunnquell CR, Vieira NA, Sábio LR, et al. Oxidative and proteolysis-related parameters of skeletal muscle from hamsters with experimental pulmonary emphysema: a comparison between papain and elastase induction. Int J Exp Pathol, 2015, 96(3): 140-150.
17.	Liu X, Ma C, Wang X, et al. Hydrogen coadministration slows the development of COPD-like lung disease in a cigarette smoke-induced rat model. Int J Chron Obstruct Pulmon Dis, 2017, 12: 1309-1324.
18.	張倩, 黃萍, 李艷, 等. 腹腔注射煙草煙霧提取物制備小鼠慢性阻塞性肺疾病模型的評價. 中華結核和呼吸雜志, 2015, 38(4): 279-285.
19.	Zhong H, Yuan P, Li Y, et al. Methionine protects mammary cells against oxidative stress through producing S-adenosylmethionine to maintain mTORC1 signaling activity. Oxid Med Cell Longev, 2021, 2021: 5550196.
20.	Taylor Levine M, Gao J, Satyanarayanan SK, et al. S-adenosyl-l-methionine (SAMe), cannabidiol (CBD), and kratom in psychiatric disorders: clinical and mechanistic considerations. Brain Behav Immun, 2020, 85: 152-161.
21.	Liu J, Huang J, Xin P, et al. Biomedical applications of methionine-based systems. Biomater Sci, 2021, 9(6): 1961-1973.

1. Taraseviciene-Stewart L, Douglas IS, Nana-Sinkam PS, et al. Is alveolar destruction and emphysema in chronic obstructive pulmonary disease an immune disease? Proc Am Thorac Soc, 2006, 3(8): 687-690.
2. Xia X, Xiang X, Huang F, et al. Dietary canolol induces apoptosis in human cervical carcinoma HeLa cells through ROS-MAPK mediated mitochondrial signaling pathway: in vitro and in vivo. Chem Biol Interact, 2019, 300: 138-150.
3. Purohit V, Abdelmalek MF, Barve S, et al. Role of S-adenosylmethionine, folate, and betaine in the treatment of alcoholic liver disease: summary of a symposium. Am J Clin Nutr, 2007, 86(1): 14-24.
4. Ara AI, Xia M, Ramani K, et al. S-adenosylmethionine inhibits lipopolysaccharide -induced gene expression via modulation of histone methylation. Hepatology, 2008, 47(5): 1655-1666.
5. 張野, 張程, 李夏, 等. SAM對大鼠自身免疫性肺氣腫氧化應激的干預. 重慶醫科大學學報, 2020, 45(11): 1528-1531.
6. He S, Li L, Sun S, et al. A novel murine chronic obstructive pulmonary disease model and the pathogenic role of microRNA-21. Front Physiol, 2018, 9: 503.
7. 張順, 楊福全, 李航宇, 等. S-腺苷甲硫氨酸對大鼠重癥急性胰腺炎的保護作用. 中國現代普通外科進展, 2011, 14(9): 680-683.
8. Li D, Li BX, Zhang Y, et al. SAM protects against alveolar septal cell apoptosis in autoimmune emphysema rats. Eur J Med Res, 2023, 28(1): 460.
9. Li N, Dai Z, Wang Z, et al. Gut microbiota dysbiosis contributes to the development of chronic obstructive pulmonary disease. Respir Res, 2021, 22(1): 274.
10. 張靜, 郭一銘, 李恩紅, 等. 甘草甜素對小鼠矽肺纖維化的干預作用. 安徽醫科大學學報, 2022, 57(1): 121-125.
11. 郭欣, 胡代菊, 梅曉冬. 煙霧暴露小鼠肺部氧化應激與炎癥的變化及戒煙的影響. 安徽醫科大學學報, 2015, 50(6): 757-760.
12. 李正歡, 張曉云, 陳楊, 等. 2020年慢性阻塞性肺疾病全球倡議《COPD診斷、治療與預防全球策略》指南解讀(一)穩定期藥物管理. 中國全科醫學, 2021, 24(8): 923-929.
13. Josephs L, Culliford D, Johnson M, et al. Improved outcomes in ex-smokers with COPD: a UK primary care observational cohort study. Eur Respir J, 2017, 49(5): 1602114.
14. Yan H, Zhao L, Wu X, et al. Inflammation and pathological damage to the lungs of mice are only partially reversed following smoking cessation on subacute exposure to cigarette smoke. Mol Med Rep, 2015, 11(6): 4246-4254.
15. De Cunto G, Bartalesi B, Cavarra E, et al. Ongoing lung inflammation and disease progression in mice after smoking cessation: beneficial effects of formyl-peptide receptor blockade. Am J Pathol, 2018, 188(10): 2195-2206.
16. Brunnquell CR, Vieira NA, Sábio LR, et al. Oxidative and proteolysis-related parameters of skeletal muscle from hamsters with experimental pulmonary emphysema: a comparison between papain and elastase induction. Int J Exp Pathol, 2015, 96(3): 140-150.
17. Liu X, Ma C, Wang X, et al. Hydrogen coadministration slows the development of COPD-like lung disease in a cigarette smoke-induced rat model. Int J Chron Obstruct Pulmon Dis, 2017, 12: 1309-1324.
18. 張倩, 黃萍, 李艷, 等. 腹腔注射煙草煙霧提取物制備小鼠慢性阻塞性肺疾病模型的評價. 中華結核和呼吸雜志, 2015, 38(4): 279-285.
19. Zhong H, Yuan P, Li Y, et al. Methionine protects mammary cells against oxidative stress through producing S-adenosylmethionine to maintain mTORC1 signaling activity. Oxid Med Cell Longev, 2021, 2021: 5550196.
20. Taylor Levine M, Gao J, Satyanarayanan SK, et al. S-adenosyl-l-methionine (SAMe), cannabidiol (CBD), and kratom in psychiatric disorders: clinical and mechanistic considerations. Brain Behav Immun, 2020, 85: 152-161.
21. Liu J, Huang J, Xin P, et al. Biomedical applications of methionine-based systems. Biomater Sci, 2021, 9(6): 1961-1973.

Chinese Journal of Respiratory and Critical Care Medicine

Effect of S-adenosyl-l-methionine on oxidative stress and alveolar septal cell apoptosis in mice with emphysema after smoking cessation

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