title: N-acetylcysteine protects rats with chronic renal failure from gadolinium-chelate nephrotoxicity.
abstract: The aim of this study was to evaluate the effect of Gd-chelate on renal function, iron parameters and oxidative stress in rats with CRF and a possible protective effect of the antioxidant N-Acetylcysteine (NAC). Male Wistar rats were submitted to 5/6 nephrectomy (Nx) to induced CRF. An ionic-cyclic Gd (Gadoterate Meglumine) was administrated (1.5 mM/KgBW, intravenously) 21 days after Nx. Clearance studies were performed in 4 groups of anesthetized animals 48 hours following Gd- chelate administration: 1--Nx (n = 7); 2--Nx+NAC (n = 6); 3--Nx+Gd (n = 7); 4--Nx+NAC+Gd (4.8 g/L in drinking water), initiated 2 days before Gd-chelate administration and maintained during 4 days (n = 6). This group was compared with a control. We measured glomerular filtration rate, GFR (inulin clearance, ml/min/kg BW), proteinuria (mg/24 hs), serum iron (µg/dL); serum ferritin (ng/mL); transferrin saturation (%), TIBC (µg/dL) and TBARS (nmles/ml). Normal rats treated with the same dose of Gd-chelate presented similar GFR and proteinuria when compared with normal controls, indicating that at this dose Gd-chelate is not nephrotoxic to normal rats. Gd-chelate administration to Nx-rats results in a decrease of GFR and increased proteinuria associated with a decrease in TIBC, elevation of ferritin serum levels, transferrin oversaturation and plasmatic TBARS compared with Nx-rats. The prophylactic treatment with NAC reversed the decrease in GFR and the increase in proteinuria and all alterations in iron parameters and TBARS induced by Gd-chelate. NAC administration to Nx rat did not modify the inulin clearance and iron kinetics, indicating that the ameliorating effect of NAC was specific to Gd-chelate. These results suggest that NAC can prevent Gd-chelate nephrotoxicity in patients with chronic renal failure.
authors: Department of Nephrology, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors: Leonardo Victor Barbosa
authors: LV
authors: Pereira
authors: Maria Heloisa Massola
authors: MH
authors: Shimizu
authors: Lina Paola Miranda Ruiz
authors: LP
authors: Rodrigues
authors: Cláudia Costa
authors: CC
authors: Leite
authors: Lúcia
authors: L
authors: Andrade
authors: Antonio Carlos
authors: AC
authors: Seguro
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D002614:Chelating Agents / Q000737:chemistry / Q000633:toxicity*; D005682:Gadolinium / Q000737:chemistry*; D005919:Glomerular Filtration Rate; D007444:Inulin / Q000493:pharmacokinetics; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D002614:Chelating Agents; D017392:Thiobarbituric Acid Reactive Substances; D007444:Inulin; D005682:Gadolinium; D000111:Acetylcysteine