title: Liver growth factor treatment reverses vascular and plasmatic oxidative stress in spontaneously hypertensive rats.
abstract: BACKGROUND
  Liver growth factor (LGF) is an albumin-bilirubin complex with antioxidant actions in vitro. In spontaneously hypertensive rats (SHRs), short LGF treatment exerts antihypertensive and antifibrotic effects.
  
  
  METHODS
  We aimed to determine if LGF treatment (4 i.p. injections, 4.5 μg/rat over 12 days) reduces oxidative stress in SHRs using Wistar-Kyoto (WKY) as control strain. We assessed the following: plasma oxidative stress biomarkers [protein-bound malondialdehyde (MDA); protein carbonyls and advanced glycation end products (AGEs)]; superoxide anion basal production in carotid artery-derived vascular smooth muscle cells (VSMCs) detected by dihydroethidium and confocal microscopy; and expression (western blot) and activities (spectroscopic methods) of NADPH and xanthine oxidases, CuZn, Mn and extracellular superoxide dismutases (SODs) and catalase in carotid arteries.
  
  
  RESULTS
  LGF treatment had the following effects: reversed the increase in plasma MDA and protein carbonyls and VSMC superoxide anion levels observed in SHRs, without any effect on WKY strain; reversed the alterations in SHR vascular p22phox expression as well as NADPH oxidase, xanthine oxidase and catalase activities; had no effect on vascular CuZn-SOD and Mn-SOD expression or total SOD activity; and reversed the elevation in SHR vascular glycated/free extracellular-SOD expression ratio and plasma glucose without changes in plasma AGEs.
  
  
  CONCLUSIONS
  LGF treatment of SHRs normalizes the level of plasma oxidative stress biomarkers through a reduction of vascular superoxide anion produced by NADPH and xanthine oxidases. These effects might be linked to the cardiovascular regenerative actions of LGF.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Condezo-Hoyos
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Arribas
authors.forename: Fátima
authors.initials: F
authors.lastname: Abderrahim
authors.forename: Beatriz
authors.initials: B
authors.lastname: Somoza
authors.forename: Marta
authors.initials: M
authors.lastname: Gil-Ortega
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Díaz-Gil
authors.forename: M Victoria
authors.initials: MV
authors.lastname: Conde
authors.forename: Cristina
authors.initials: C
authors.lastname: Susin
authors.forename: M Carmen
authors.initials: MC
authors.lastname: González
mesh_terms: D000818:Animals; D001663:Bilirubin / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D002374:Catalase / Q000097:blood / Q000378:metabolism; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012709:Serum Albumin / Q000494:pharmacology / Q000627:therapeutic use*; D000075462:Serum Albumin, Human; D013482:Superoxide Dismutase / Q000097:blood / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014969:Xanthine Oxidase / Q000097:blood / Q000378:metabolism
chemical_list: D012709:Serum Albumin; C053498:albumin-bilirubin complex; D013481:Superoxides; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D019255:NADPH Oxidases; D001663:Bilirubin; D000075462:Serum Albumin, Human