title: Azilsartan improves glycemic status and reduces kidney damage in zucker diabetic fatty rats.
abstract: BACKGROUND
  Azilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, demonstrates antihypertensive and organ protective effects in hypertension. We investigated the efficacy of AZL-M to ameliorate metabolic syndrome and kidney damage associated with type 2 diabetes using Zucker diabetic fatty (ZDF) rats.
  
  
  METHODS
  ZDF rats were treated with vehicle or AZL-M for 8 weeks. Zucker diabetic lean (ZDL) rats were used as controls. Urine and plasma samples were collected for biochemical analysis, and kidney tissues were used for histopathological and immunohistopathological examination at the end of the 8-week protocol.
  
  
  RESULTS
  ZDF rats were diabetic with hyperglycemia and impaired glucose tolerance, and AZL-M ameliorated the diabetic phenotype. ZDF rats were hypertensive compared with ZDL rats (181±6 vs. 129±7mm Hg), and AZL-M decreased blood pressure in ZDF rats (116±7mm Hg). In ZDF rats, there was marked renal damage with elevated proteinuria, albuminuria, nephrinuria, 2-4-fold higher tubular cast formation, and glomerular injury compared with ZDL rats. AZL-M treatment reduced renal damage in ZDF rats. ZDF rats demonstrated renal inflammation and oxidative stress with elevated urinary monocyte chemoattractant protein 1 excretion, renal infiltration of macrophages, and elevated kidney malondialdehyde levels. AZL-M reduced oxidative stress and inflammation in ZDF rats.
  
  
  CONCLUSIONS
  Overall, we demonstrate that AZL-M attenuates kidney damage in type 2 diabetes. We further demonstrate that anti-inflammatory and antioxidative activities of AZL-M contribute to its kidney protective action.
authors.affiliation: Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin;
authors.forename: Md Abdul
authors.initials: MA
authors.lastname: Hye Khan
authors.affiliation: Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin; Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic;
authors.forename: Jan
authors.initials: J
authors.lastname: Neckář
authors.affiliation: Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin;
authors.forename: Jasmine
authors.initials: J
authors.lastname: Haines
authors.affiliation: Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin. jdimig@mcw.edu.
authors.forename: John D
authors.initials: JD
authors.lastname: Imig
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D003928:Diabetic Nephropathies / Q000473:pathology / Q000517:prevention & control*; D004730:Endothelium, Vascular / Q000187:drug effects; D018149:Glucose Intolerance / Q000517:prevention & control; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000188:drug therapy; D008297:Male; D010069:Oxadiazoles / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011924:Rats, Zucker
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001786:Blood Glucose; D010069:Oxadiazoles; C521273:azilsartan
keywords: azilsartan medoxomil; blood pressure; hypertension; inflammation; kidney injury; oxidative stress; type 2 diabetes.