title: Telmisartan attenuates diabetic nephropathy by suppressing oxidative stress in db/db mice.
abstract: OBJECTIVE
  Telmisartan, an angiotensin II type 1 receptor blocker, is widely used to treat hypertension and kidney diseases, including diabetic nephropathy, because of its renoprotective effects. However, the mechanism by which telmisartan prevents proteinuria and renal dysfunction in diabetic nephropathy is still unclear. In this study, we examined the effects of telmisartan against diabetic nephropathy in db/db mice.
  
  
  METHODS
  Telmisartan was administered at a dose of 5 mg/kg/day for 3 weeks to db/db (diabetic) and db/m (control) mice. Urinary albumin excretion, renal histology, and the gene expression of oxidative stress and inflammatory markers in renal tissue were determined. To evaluate the effects of telmisartan on reactive oxygen species (ROS) production, superoxide was detected by dihydroethidium (DHE) staining in vivo and in vitro.
  
  
  RESULTS
  Telmisartan reduced albuminuria, mesangial matrix expansion, macrophage infiltration, and the expression of ROS markers (NADPH oxidase 4- and 8-hydroxydeoxyguanosine) and inflammatory cytokines (monocyte chemoattractant protein-1, osteopontin, and transforming growth factor-β) in the kidney. DHE staining showed that telmisartan decreased ROS generation in the kidney and in cultured mesangial and proximal tubular epithelial cells.
  
  
  CONCLUSIONS
  Taken together, these findings indicate that telmisartan protects against diabetic nephropathy by reducing diabetes-induced oxidative stress.
authors.affiliation: Department of Medicine and Clinical Science, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan.
authors.forename: Chikage
authors.initials: C
authors.lastname: Sato-Horiguchi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ogawa
authors.forename: Jun
authors.initials: J
authors.lastname: Wada
authors.forename: Hiromi
authors.initials: H
authors.lastname: Tachibana
authors.forename: Ryo
authors.initials: R
authors.lastname: Kodera
authors.forename: Jun
authors.initials: J
authors.lastname: Eguchi
authors.forename: Atsuko
authors.initials: A
authors.lastname: Nakatsuka
authors.forename: Naoto
authors.initials: N
authors.lastname: Terami
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shikata
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Makino
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use*; D001565:Benzoates / Q000494:pharmacology* / Q000627:therapeutic use*; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008815:Mice, Inbred Strains; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077333:Telmisartan
chemical_list: D001562:Benzimidazoles; D001565:Benzoates; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; D000077333:Telmisartan