title: Protective effect of melatonin on the development of abdominal aortic aneurysm in a rat model.
abstract: Oxidative injury, inflammation, and apoptosis are involved in the progression of abdominal aortic aneurysm (AAA). Melatonin (MLT) has been reported with an effective antioxidant activity. The objective of the present study was to investigate whether MLT could suppress the development of AAA.
  
  
  
  The AAA model was introduced by intraluminal perfusion of elastase in rats. All rats were divided into three groups as follows: (1) sham; (2) AAA + vehicle; and (3) AAA + MLT. Daily administration of MLT (10 mg/kg/d) or vehicle started 3 d before the perfusion and continued for 28 d after perfusion. An ultrasound system was applied to measure the dilation of the aorta. Histologic assays were performed to evaluate the structure, morphology, and apoptotic cells of the aortas; biochemical assays to determine the levels of proteins and lipid peroxide, activities of superoxide dismutase and NADPH oxidases, and cell viability; dihydroethidium fluorescence staining and flow cytometry to detect the presence of reactive oxygen species, and/or cell apoptosis; and electron microscopy to observe the ultrastructure of mitochondria. Cell lines A7R5 and RAW 264.7 were used for in vitro experiments.
  
  
  
  MLT treatment inhibited dilation of the aorta very likely through its antioxidant property; significantly reduced the levels of lipid peroxide, activities of NADPH oxidases, and content of reactive oxygen species; remarkably inhibited NF-κB signaling pathway and activities of matrix metalloproteinases triggered by elastase perfusion. As a result, the mitochondrion-dependent apoptosis was suppressed, cellular energy (ATP) supply was recovered, and mitochondrial morphology remained intact.
  
  
  
  Our results demonstrate the beneficial effects of MLT on inhibition of AAA formation, suggesting that MLT could be a potential agent for prevention of the development of human AAA.
authors.affiliation: Department of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Zhuangzhuang
authors.initials: Z
authors.lastname: Cong
authors.affiliation: Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China.
authors.forename: Shuangying
authors.initials: S
authors.lastname: Hao
authors.affiliation: Department of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Hairong
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. Electronic address: dr.shenyi@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, China. Electronic address: likuanyu@nju.edu.cn.
authors.forename: Kuanyu
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Cardiothoracic Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. Electronic address: 15850728068@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Jing
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001012:Aorta, Abdominal / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000473:pathology / Q000517:prevention & control*; D017209:Apoptosis / Q000187:drug effects; D007249:Inflammation / Q000517:prevention & control; D008297:Male; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D008928:Mitochondria / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010196:Pancreatic Elastase; D011897:Random Allocation; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D010196:Pancreatic Elastase; D008550:Melatonin
keywords: Abdominal aortic aneurysm; Apoptosis; Melatonin; Mitochondria; NF-κB; Oxidative stress