title: Low molecular weight fucoidan ameliorates streptozotocin-induced hyper-responsiveness of aortic smooth muscles in type 1 diabetes rats.
abstract: BACKGROUND
  Low molecular weight fucoidan (LMWF) was prepared from Laminaria japonica Areschoug, a popular seafood and medicinal plant consumed in Asia. Chinese have long been using it as a traditional medicine for curing hypertension and edema.
  
  
  OBJECTIVE
  This study was intent to investigate the possible beneficial effect of LMWF on hyper-responsiveness of aortic smooth muscles instreptozotocin (STZ)-induced type 1 diabetic rats.
  
  
  METHODS
  Sprague-Dawley rats were made diabetic by injection of STZ, followed by the administration of LMWF (50 or 100mg/kg/day) or probucol (100mg/kg/day) for 12 weeks. Body weight, blood glucose level, basal blood pressure, serum lipid profiles, oxidative stress, prostanoids production, and vasoconstriction response of endothelium-denuded aorta rings to phenylephrine were measured by Real time-PCR, Western blots, ELISA assay, and force myograph, respectively.
  
  
  RESULTS
  LMWF (100mg/kg/day)-treated group showed robust improvements on STZ-induced body weight-loss, hypertension, and hyperlipidaemia as indicated by decreased serum level of total cholesterol, triglyceride, and low density lipoprotein cholesterol; while probucol, a lipid-modifying drug with antioxidant properties, displayed mild effects. In addition, LMWF appreciably ameliorated STZ-elicited hyper-responsiveness and oxidative stress in aortic smooth muscles as indicated by decreased superoxide level, increased glutathione content and higher superoxide dismutase activity. Furthermore, administration with LMWF dramatically prevented cyclooxygenase-2 stimulation and restored the up-regulation of thromboxane synthase and down-regulation of 6-keto-PGF1α (a stable metabolic product of prostaglandin I2) in the STZ-administered rats.
  
  
  CONCLUSIONS
  This study demonstrates for the first time that LMWF can protect against hyperlipidaemia, hypertension, and hyper-responsiveness of aortic smooth muscles in type 1 diabetic rat via, at least in part, amelioration of oxidative stress and restoration of prostanoids levels in aortic smooth muscles. Therefore, LMWF can be a potential adjuvant treatment against cardiovascular complications in type 1 diabetes.
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing 100069, PR China. Electronic address: nxsmzwnemhds@126.com.
authors.forename: Zhengyang
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing 100069, PR China. Electronic address: zhengyy99@hotmail.com.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, PR China. Electronic address: jingwang@qdio.ac.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, PR China. Electronic address: qbzhang@qdio.ac.cn.
authors.forename: Quanbin
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing 100069, PR China. Electronic address: renshuang12@126.com.
authors.forename: Shuang
authors.initials: S
authors.lastname: Ren
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing 100069, PR China. Electronic address: liutiantian008@126.com.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing 100069, PR China. Electronic address: zhiqiang3250101@126.com.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing 100069, PR China. Electronic address: luodl@ccmu.edu.cn.
authors.forename: Dali
authors.initials: D
authors.lastname: Luo
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D006949:Hyperlipidemias / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control*; D006973:Hypertension / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control*; D000960:Hypolipidemic Agents / Q000737:chemistry / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008297:Male; D008970:Molecular Weight; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013311:Streptozocin; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D001786:Blood Glucose; D000960:Hypolipidemic Agents; D008055:Lipids; D011134:Polysaccharides; D011453:Prostaglandins; D013481:Superoxides; D013311:Streptozocin; C007789:fucoidan; D013482:Superoxide Dismutase; D005978:Glutathione
keywords: Aorta; Diabetes; Fucoidan; Hypertension; Vascular smooth muscles