title: Resveratrol ameliorates renal damage, increases expression of heme oxygenase-1, and has anti-complement, anti-oxidative, and anti-apoptotic effects in a murine model of membranous nephropathy.
abstract: BACKGROUND
  Idiopathic membranous nephropathy (MN) is an autoimmune-mediated glomerulonephritis and a common cause of nephrotic syndrome in adults. There are limited available treatments for MN. We assessed the efficacy of resveratrol (RSV) therapy for treatment of MN in a murine model of this disease.
  
  
  METHODS
  Murine MN was experimentally induced by daily subcutaneous administration of cationic bovine serum albumin, with phosphate-buffered saline used in control mice. MN mice were untreated or given RSV. Disease severity and pathogenesis was assessed by determination of metabolic and histopathology profiles, lymphocyte subsets, immunoglobulin production, oxidative stress, apoptosis, and production of heme oxygenase-1 (HO1).
  
  
  RESULTS
  MN mice given RSV had significantly reduced proteinuria and a marked amelioration of glomerular lesions. RSV also significantly attenuated immunofluorescent staining of C3, although there were no changes of serum immunoglobulin levels or immunocomplex deposition in the kidneys. RSV treatment of MN mice also reduced the production of reactive oxygen species (ROS), reduced cell apoptosis, and upregulated heme oxygenase 1 (HO1). Inhibition of HO1 with tin protoporphyrin IX partially reversed the renoprotective effects of RSV. The HO1 induced by RSV maybe via Nrf2 signaling.
  
  
  CONCLUSIONS
  Our results show that RSV increased the expression of HO1 and ameliorated the effects of membranous nephropathy in a mouse model due to its anti-complement, anti-oxidative, and anti-apoptotic effects. RSV appears to have potential as a treatment for MN.
authors.affiliation: Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chia-Chao
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Yen-Sung
authors.initials: YS
authors.lastname: Huang
authors.affiliation: Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Jin-Shuen
authors.initials: JS
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Huang
authors.affiliation: School of Public Health, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Sui-Lung
authors.initials: SL
authors.lastname: Su
authors.affiliation: Department of Medicine, Cardinal Tien Hospital, School of Medicine, Fu Jen Catholic University, New Taipei city, Taiwan.
authors.forename: Kuo-Cheng
authors.initials: KC
authors.lastname: Lu
authors.affiliation: Division of Nephrology, Department of Medicine, Shuang-Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yuh-Feng
authors.initials: YF
authors.lastname: Lin
authors.affiliation: Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Pauling
authors.initials: P
authors.lastname: Chu
authors.affiliation: Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shih-Hua
authors.initials: SH
authors.lastname: Lin
authors.affiliation: Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Huey-Kang
authors.initials: HK
authors.lastname: Sytwu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D003165:Complement System Proteins / Q000187:drug effects; D004195:Disease Models, Animal; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics; D007668:Kidney / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D008665:Metalloporphyrins / Q000008:administration & dosage; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D011524:Protoporphyrins / Q000008:administration & dosage; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D012709:Serum Albumin / Q000008:administration & dosage; D013267:Stilbenes / Q000008:administration & dosage*
chemical_list: D008665:Metalloporphyrins; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; D012709:Serum Albumin; D013267:Stilbenes; D003165:Complement System Proteins; C032628:tin protoporphyrin IX; D051547:Heme Oxygenase-1; D000077185:Resveratrol