title: Effective Delivery of Endogenous Antioxidants Ameliorates Diabetic Nephropathy.
abstract: BACKGROUND
  Diabetic nephropathy (DN) is thought to be partially due to the injury of renal cells and the renal micro-environment by free radicals. Free radial scavenging agents that inhibit free radical damage may well prevent the development of underlying conditions such as mesangial expansion (by inhibiting extracellular matrix expression) in these patients.
  
  
  METHODS
  Using techniques for intra-cellular delivery of peptides, we made metallothionein (MT) and superoxide dismutase (SOD), potent endogenous antioxidants, readily transducible into cell membrane and tested their protective effect against the development of DN in OLETF rats. Herein, we study antioxidant peptides for their ability to prevent oxidative damage to primary rat mesangial cells (MCs), which are important constituents of renal glomeruli.
  
  
  RESULTS
  Intraperitoneal administration of these antioxidants resulted in delivery to the kidney and decreased ROS and the expression of downstream signals in renal cells and postponed the usual progression to DN. In in vitro experiments, MT and SOD were efficiently transferred to MCs, and the increased removal of ROS by MT and SOD was proportional to the degree of scavenging enzymes delivered. MT and SOD decreased three major oxidative injuries (hyperglycemia, AGE and ROS exposure) and also injuries directly mediated by angiotensin II in MCs while changing downstream signal transduction.
  
  
  CONCLUSIONS
  The protective effects of MT and SOD for the progression of DN in experimental animals may be associated with the scavenging of ROS by MT and SOD and correlated changes in signal transduction downstream. Concomitant administration of these antioxidant peptides may prove to be a new approach for the prevention and therapy of DN.
authors.affiliation: Department of Internal Medicine and Bioengineering, Hanyang University College of Medicine and Engineering, Seoul, Korea.
authors.forename: Yongsoo
authors.initials: Y
authors.lastname: Park
authors.affiliation: Department of Internal Medicine and Bioengineering, Hanyang University College of Medicine and Engineering, Seoul, Korea.
authors.forename: Hyunok
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine and Bioengineering, Hanyang University College of Medicine and Engineering, Seoul, Korea.
authors.forename: Leejin
authors.initials: L
authors.lastname: Park
authors.affiliation: Department of Internal Medicine and Bioengineering, Hanyang University College of Medicine and Engineering, Seoul, Korea.
authors.forename: Dongsoo
authors.initials: D
authors.lastname: Min
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon, Korea.
authors.forename: Jinseu
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon, Korea.
authors.forename: Sooyoung
authors.initials: S
authors.lastname: Choi
authors.affiliation: Department of Pathology, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Moon Hyang
authors.initials: MH
authors.lastname: Park
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008297:Male; D050527:Mesangial Cells / Q000378:metabolism / Q000473:pathology; D008668:Metallothionein / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D013482:Superoxide Dismutase / Q000494:pharmacology*
chemical_list: D016166:Free Radical Scavengers; D010455:Peptides; D008668:Metallothionein; D013482:Superoxide Dismutase