title: Oleanolic acid and N-acetylcysteine ameliorate diabetic nephropathy through reduction of oxidative stress and endoplasmic reticulum stress in a type 2 diabetic rat model.
abstract: BACKGROUND
  Hyperglycemia-induced endoplasmic reticulum (ER) stress and oxidative stress could be causes of renal fibrosis in diabetes. Oleanolic acid (OA) naturally occurs in fruits and vegetables. It has anti-inflammatory, antihyperlipidemic and antioxidant effects. N-acetylcysteine (NAC) is a precursor of glutathione, which has a strong antioxidant effect in the body. In this study, we investigated the therapeutic effects of OA and NAC in diabetic nephropathy (DN).
  
  
  METHODS
  Otsuka Long-Evans Tokushima Fatty rats were treated with OA (100 mg/kg/day) or NAC (300 mg/kg/day) for 20 weeks by oral gavage.
  
  
  RESULTS
  The OA or NAC administration increased blood insulin secretion and superoxide dismutase levels, and decreased triglycerides and urinary albumin/creatinine levels. In the kidney, the damaged renal structure recovered with OA or NAC administration, through an increase in nephrin and endothelial selective adhesion molecules and a decrease in transforming growth factor-β/p-smad2/3 and ER stress. Reactive oxygen species and ER stress were increased by high glucose and ER stress inducers in cultured mesangial cells, and these levels recovered with OA (5.0 μM) or NAC (2.5 mM) treatment.
  
  
  CONCLUSIONS
  The findings in this study suggest that OA and NAC have therapeutic effects for DN through an antioxidant effect and ER stress reduction.
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, 162 Ilsan-Dong, Wonju, Gangwon-Do 220-701, Republic of Korea.
authors.forename: Eun Soo
authors.initials: ES
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, 162 Ilsan-Dong, Wonju, Gangwon-Do 220-701, Republic of Korea.
authors.forename: Hong Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 330-721, Republic of Korea.
authors.forename: Jeong Suk
authors.initials: JS
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 330-721, Republic of Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, 162 Ilsan-Dong, Wonju, Gangwon-Do 220-701, Republic of Korea.
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Yadav
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, 162 Ilsan-Dong, Wonju, Gangwon-Do 220-701, Republic of Korea.
authors.forename: Mi-Hye
authors.initials: MH
authors.lastname: Kwon
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, 162 Ilsan-Dong, Wonju, Gangwon-Do 220-701, Republic of Korea.
authors.forename: You Mi
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Republic of Korea.
authors.forename: Hyeon Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, 162 Ilsan-Dong, Wonju, Gangwon-Do 220-701, Republic of Korea.
authors.forename: Choon Hee
authors.initials: CH
authors.lastname: Chung
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D003921:Diabetes Mellitus, Experimental; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D020334:Rats, Inbred OLETF; D017382:Reactive Oxygen Species
chemical_list: D017382:Reactive Oxygen Species; D000111:Acetylcysteine
keywords: ER stress; N-acetylcysteine; diabetic nephropathy; oleanolic acid; oxidative stress