Nephrol Dial Transplant (2000) 15: 467-476
© 2000 European Renal Association-European Dialysis and Transplant Association
Oxidative stress occurs in absence of hyperglycaemia and inflammation in the onset of kidney lesions in normotensive obese rats
1 INSERM U 430, Broussais Hospital, and Claude Bernard Association, Paris, 2 Laboratory of Biochemistry, Bicêtre Hospital, 3 INSERM U 465, Institut des Cordeliers, Paris and 4 Laboratory of Applied Biochemistry, Faculty of Pharmaceutical and Biological Sciences, Châtenay-Malabry, France
Correspondence and offprint requests to: Dr Jacques Chevalier, Immunopathologie Rénale et Vasculaire, INSERM U 430, Hôpital Broussais, 96 Rue Didot, F-75674 Paris CEDEX 14, France.
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-ED1+-cell infiltration. At 6 months and thereafter, kidney lesions and functional impairment worsened while numerous ED1+-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 (H2O2). 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.
Conclusion. 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.
Keywords: glomerulosclerosis; hyperinsulinaemia; lipid peroxidation; obesity; Zucker rat
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