title: Carnosine prevents apoptosis of glomerular cells and podocyte loss in STZ diabetic rats.
abstract: OBJECTIVE
  We identified carnosinase-1 (CN-1) as risk-factor for diabetic nephropathy (DN). Carnosine, the substrate for CN-1, supposedly is a protective factor regarding diabetic complications. In this study, we hypothesized that carnosine administration to diabetic rats might protect the kidneys from glomerular apoptosis and podocyte loss.
  
  
  METHODS
  We examined the effect of oral L-carnosine administration (1g/kg BW per day) on apoptosis, podocyte loss, oxidative stress, AGEs and hexosamine pathway in kidneys of streptozotocin-induced diabetic Wistar rats after 3 months of diabetes and treatment.
  
  
  RESULTS
  Hyperglycemia significantly reduced endogenous kidney carnosine levels. In parallel, podocyte numbers significantly decreased (-21% compared to non-diabetics, p<0.05), apoptotic glomerular cells numbers increased (32%, compared to non-diabetic, p<0.05) and protein levels of bax and cytochrome c increased (175% and 117%). Carnosine treatment restored carnosine kidney levels, prevented podocytes loss (+23% compared to diabetic, p<0.05), restrained glomerular apoptosis (-34% compared to diabetic; p<0.05) and reduced expression of bax and cytochrome c (-63% and -54% compared to diabetics, both p<0.05). In kidneys of all diabetic animals, levels of ROS, AGEs and GlcNAc-modified proteins were increased.
  
  
  CONCLUSIONS
  By inhibition of pro-apoptotic signaling and independent of biochemical abnormalities, carnosine protects diabetic rat kidneys from apoptosis and podocyte loss.
authors.affiliation: 5th Medical Clinic, University Medicine Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Riedl
authors.forename: Frederick
authors.initials: F
authors.lastname: Pfister
authors.forename: Margarita
authors.initials: M
authors.lastname: Braunagel
authors.forename: Paul
authors.initials: P
authors.lastname: Brinkkötter
authors.forename: Paula
authors.initials: P
authors.lastname: Sternik
authors.forename: Martina
authors.initials: M
authors.lastname: Deinzer
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.forename: Rob H
authors.initials: RH
authors.lastname: Henning
authors.forename: Jacob
authors.initials: J
authors.lastname: van den Born
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Krämer
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hammes
authors.forename: Benito
authors.initials: B
authors.lastname: Yard
authors.forename: Hannes
authors.initials: H
authors.lastname: Koeppel
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002336:Carnosine / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D017127:Glycation End Products, Advanced / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D050199:Podocytes / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013311:Streptozocin / Q000633:toxicity; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D013311:Streptozocin; D002336:Carnosine; D045304:Cytochromes c; D000117:Acetylglucosamine