title: Oxidative stress occurs in absence of hyperglycaemia and inflammation in the onset of kidney lesions in normotensive obese rats.
abstract: BACKGROUND
  Several factors favour the development of kidney lesions. We examined the role of oxidative stress in the onset of renal alterations that occur in Zucker obese (ZO) fa/fa rats.
  
  
  METHODS
  Kidney structure, biological data, glycation parameters, advanced glycation end products (AGE), thiobarbituric acid-reactive substances (TBARS), circulating antibodies anti-malondialdehyde (MDA)-modified low-density lipoprotein (LDL), antioxidant defenses (Cu/Zn and Mn superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) activities, glutathione level), were determined in plasma and/or kidney of young and old ZO rats and lean (ZL) Fa/fa littermates.
  
  
  RESULTS
  Renal lesions and functional decline appeared at 3 months in hyperlipidaemic, hyperinsulinaemic, normotensive ZO rats, independently of any macrophage-ED(1)(+)-cell infiltration. At 6 months and thereafter, kidney lesions and functional impairment worsened while numerous ED(1)(+)-cells invaded the interstitium. At 3 and 9 months, TBARS level in the LDL/very low-density lipoprotein fraction and in the kidney was higher in ZO than in ZL rats. Anti-MDA-LDL antibodies were increased in ZO rats. At 3 months, renal activity of Cu/Zn SOD was higher, and activities of catalase and GPx lower in ZO than in ZL rats, leading to an accumulation of hydrogen peroxide (H(2)O(2)). At 9 months, a decrease in Cu/Zn SOD activity and an increase in glutathione level were observed. Blood glucose and glycated proteins, as well as AGE in kidney, remained similar in both ZL and ZO rats, whatever their age.
  
  
  CONCLUSIONS
  These data suggest that oxidative stress triggers, at an early age, the onset of kidney lesions and functional impairment in ZO rats, in absence of hyperglycaemia, hypertension and inflammation.
authors.affiliation: INSERM U 430, Broussais Hospital, and Claude Bernard Association, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Poirier
authors.forename: M
authors.initials: M
authors.lastname: Lannaud-Bournoville
authors.forename: M
authors.initials: M
authors.lastname: Conti
authors.forename: R
authors.initials: R
authors.lastname: Bazin
authors.forename: O
authors.initials: O
authors.lastname: Michel
authors.forename: J
authors.initials: J
authors.lastname: Bariéty
authors.forename: J
authors.initials: J
authors.lastname: Chevalier
authors.forename: I
authors.initials: I
authors.lastname: Myara
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology*; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D005355:Fibrosis; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006442:Glycated Hemoglobin / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006031:Glycosylation; D006943:Hyperglycemia / Q000097:blood*; D007249:Inflammation; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D011924:Rats, Zucker; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D014563:Urodynamics
chemical_list: D001786:Blood Glucose; D002784:Cholesterol; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides