title: Ginseng treatment attenuates chronic cyclosporine nephropathy via reducing oxidative stress in an experimental mouse model.
abstract: BACKGROUND
  This study was performed to investigate whether ginseng extract has a protective effect in an experimental mouse model of chronic cyclosporine (CsA) nephropathy.
  
  
  METHODS
  Mice were treated with CsA (30 mg/kg/day, subcutaneously) with or without Korean red ginseng extract (KRG) (0.2, 0.4 g/kg/day, orally) on a 0.01% salt diet for 4 weeks. The effect of KRG on CsA-induced renal injury was evaluated by assessing renal function and pathology, mediators of inflammation, tubulointerstitial fibrosis and apoptotic cell death. Using an in vitro model, we also examined the effect of KRG on CsA-treated proximal tubular cells (HK-2). Oxidative stress was measured by assessing 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in 24-hour urine, tissue sections, and culture media.
  
  
  RESULTS
  Four weeks of CsA treatment caused renal dysfunction, typical pathologic lesions and apoptotic cell death. KRG treatment reduced serum creatinine and blood urea nitrogen and histopathology and increased creatinine clearance. Proinflammatory and profibrotic molecules such as induced nitric oxide synthase, cytokines, transforming growth factor (TGF)-β1 and TGF-β1-inducible gene h3 and apoptotic cell death, also decreased with KRG treatment. Consistent with these results, in vitro studies showed that addition of KRG protected against CsA-induced morphological changes, cytotoxicity, inflammation, and apoptotic cell death as demonstrated by annexin V binding. These changes were accompanied by decrease in the level of 8-OHdG in urine and culture supernatant after KRG treatment.
  
  
  CONCLUSIONS
  The results of our in vivo and in vitro studies demonstrate that KRG has a protective effect in CsA-induced renal injury via reducing oxidative stress.
authors.affiliation: Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, Seoul, Korea.
authors.forename: Kyoung Chan
authors.initials: KC
authors.lastname: Doh
authors.forename: Sun Woo
authors.initials: SW
authors.lastname: Lim
authors.forename: Shang Guo
authors.initials: SG
authors.lastname: Piao
authors.forename: Long
authors.initials: L
authors.lastname: Jin
authors.forename: Seong Beom
authors.initials: SB
authors.lastname: Heo
authors.forename: Yu Fen
authors.initials: YF
authors.lastname: Zheng
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Bae
authors.forename: Gyu Hyun
authors.initials: GH
authors.lastname: Hwang
authors.forename: Kyoung Il
authors.initials: KI
authors.lastname: Min
authors.forename: Byung Ha
authors.initials: BH
authors.lastname: Chung
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Yang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D016572:Cyclosporine / Q000009:adverse effects*; D041743:Herb-Drug Interactions; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D005894:Panax; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D010936:Plant Extracts; D016572:Cyclosporine