title: Anti-oxidative effect of vitamin D analog on incipient vascular lesion in non-obese type 2 diabetic rats.
abstract: OBJECTIVE
  Vascular disease is one of the critical complications of diabetes. A growing body of evidence suggests that oxidative stress plays a key role for vascular disease progression. Recent studies have demonstrated a strong link between vitamin D and cardiovascular disease.
  
  
  METHODS
  We investigated the anti-oxidative effects of a vitamin D analog, 22-oxacalcitriol (maxacalcitol), on vascular lesions in type 2 diabetic rats. We used Spontaneously Diabetic Torii (SDT) rats, a model of non-obese type 2 diabetes. At 20 weeks of age, SDT rats were randomly divided into three groups: diabetes mellitus (DM, n = 10), DM + maxacalcitol (DM + D, n = 10), and DM + insulin (DM + I, n = 10). The rats were sacrificed at 30 weeks for the evaluation of blood and urine samples as well as histopathology and mRNA expression in the aorta.
  
  
  RESULTS
  Urinary 8-hydroxydeoxyguanosine (8-OHdG) excretion and the number of 8-OHdG-positive cells were significantly lower in the DM + I and DM + D groups than in the DM group. Real-time polymerase chain reaction analysis demonstrated that NADPH p22 phox and NADPH p47 phox mRNA levels were markedly decreased in the DM + I and DM + D groups compared with the DM group. Furthermore, the mRNA expression of MCP-1, ICAM-1 and VCAM-1 was significantly reduced in the DM + I and DM + D groups compared with the DM group.
  
  
  CONCLUSIONS
  Our results suggest that the vasoprotective effects of vitamin D are mediated by reducing oxidative stress.
authors: Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Keiji
authors: K
authors: Kono
authors: Hideki
authors: H
authors: Fujii
authors: Kentaro
authors: K
authors: Nakai
authors: Shunsuke
authors: S
authors: Goto
authors: Riko
authors: R
authors: Kitazawa
authors: Sohei
authors: S
authors: Kitazawa
authors: Masami
authors: M
authors: Shinohara
authors: Michinori
authors: M
authors: Hirata
authors: Masafumi
authors: M
authors: Fukagawa
authors: Shinichi
authors: S
authors: Nishi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D002097:C-Reactive Protein / Q000378:metabolism; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D018932:Chemokine CCL2 / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D007328:Insulin / Q000627:therapeutic use; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007375:Interleukin-1 / Q000097:blood; D019255:NADPH Oxidases / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics; D014652:Vascular Diseases / Q000209:etiology
chemical_list: D000975:Antioxidants; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D007328:Insulin; D007375:Interleukin-1; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002097:C-Reactive Protein; D019255:NADPH Oxidases; C515768:Cyba protein, rat; C060505:neutrophil cytosolic factor 1; D002117:Calcitriol; D003849:Deoxyguanosine; C051883:maxacalcitol