title: The protective effect of melatonin on smoke-induced vascular injury in rats and humans: a randomized controlled trial.
abstract: Smoking is one of the most harmful lifestyles in the world. Very few studies have investigated the effects of melatonin in smoke-induced vascular injury. This study was designed to investigate whether melatonin could protect rats and humans from smoke-induced vascular injury. 32 male rats and a double-blind randomized controlled trial (RCT) containing 63 participants formed the subjects of this study. In rats, 10 mg/kg of melatonin was intraperitoneally injected. Blood samples and abdominal artery were harvested two weeks later. Melatonin decreased the expression of platelet endothelial cell adhesion molecule-1 (CD31), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelin-1 (ET-1) compared with the smoke exposed group (P < 0.05), whereas endothelial nitric oxide synthase (eNOS), nuclear erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO-1), catalytic glutamate cysteine ligase (GCLC) and heme oxygenase-1 (HO-1) recovered markedly (P < 0.05). In humans, 3 mg/day of melatonin was taken orally by the participants. Blood samples were drawn at baseline and after two weeks of treatment. Compared with the oral placebo group, melatonin decreased the concentration of fibrinogen (Fbg) (P = 0.04) and free fatty acids (FFA) (P = 0.04) in smokers, along with the decreased expression of ICAM-1, VCAM-1 and ET-1 (P = 0.004, P = 0.001, P < 0.0001, respectively). In contrast, Nrf2 and HO-1 expression were markedly increased (P = 0.0001, P = 0.0049, respectively) after smokers took melatonin orally. In summary, our present data suggest that melatonin could ameliorate smoke-induced vascular injury.
authors.affiliation: Department of Vascular Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Zhanqi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Vascular Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Leng
authors.initials: L
authors.lastname: Ni
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Pathophysiology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Vascular Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Chengran
authors.initials: C
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Pathophysiology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Ren
authors.affiliation: Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Vascular Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Changwei
authors.initials: C
authors.lastname: Liu
mesh_terms: D000328:Adult; D000818:Animals; D005260:Female; D006801:Humans; D008297:Male; D051381:Rats; D000284:Administration, Oral; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D019332:Endothelin-1 / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000096:biosynthesis; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D008550:Melatonin / Q000008:administration & dosage; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D017207:Rats, Sprague-Dawley; D012907:Smoking / Q000009:adverse effects / Q000188:drug therapy / Q000378:metabolism; D014652:Vascular Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D019332:Endothelin-1; C000609392:GCLC protein, human; C544143:GCLC protein, rat; D005721:Glutamate-Cysteine Ligase; D051547:Heme Oxygenase-1; C496541:HMOX1 protein, human; D008550:Melatonin; D016660:NAD(P)H Dehydrogenase (Quinone); D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D052250:Nitric Oxide Synthase Type III; C496314:NOS3 protein, human; C496316:Nos3 protein, rat; C447479:NQO1 protein, human; C507703:NQO1 protein, rat
keywords: cigarette smoke; melatonin; vascular injury