Aldose reductase inhibition counteracts nitrosative stress and poly(ADP-ribose) polymerase activation in diabetic rat kidney and high-glucose-exposed human mesangial cells

• Published in: Free radical biology & medicine 2006-04, Vol.40 (8), p.1454-1465
• Main Authors: Drel, Viktor R., Pacher, Pal, Stevens, Martin J., Obrosova, Irina G.
• Format: Article
• Language: English
• Subjects: Aldehyde Reductase - antagonists & inhibitors; Aldehyde Reductase - metabolism; Aldose reductase; Animals; Body Weight - drug effects; Diabetes Mellitus, Experimental - enzymology; Diabetes Mellitus, Experimental - pathology; Enzyme Activation - drug effects; Fidarestat; Free radicals; Glucose - metabolism; Glucose - pharmacology; Immunohistochemistry; Kidney - drug effects; Kidney - enzymology; Male; Mesangial Cells - cytology; Mesangial Cells - drug effects; Mesangial Cells - enzymology; Nitrogen - chemistry; Nitrogen - metabolism; Oxidation-Reduction; Oxidative-nitrosative stress; Poly(ADP-ribose) polymerase; Poly(ADP-ribose) Polymerases - metabolism; Rats; Rats, Wistar; Streptozotocin-diabetic rats; Superoxide; Tyrosine - analogs & derivatives; Tyrosine - metabolism
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2005.12.034

Both increased aldose reductase (AR) activity and oxidative/nitrosative stress have been implicated in the pathogenesis of diabetic nephropathy, but the relation between the two factors remains a subject of debate. This study evaluated the effects of AR inhibition on nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation in diabetic rat kidney and high-glucose-exposed human mesangial cells. In animal experiments, control (C) and streptozotocin-diabetic (D) rats were treated with/without the AR inhibitor fidarestat (F, 16 mg kg −1 day −1) for 6 weeks starting from induction of diabetes. Glucose, sorbitol, and fructose concentrations were significantly increased in the renal cortex of D vs C ( p