N-Acetylcysteine Protects Rats with Chronic Renal Failure from Gadolinium-Chelate Nephrotoxicity

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 (mu g/dL); serum ferritin (ng/mL); transferrin saturation (%), TIBC (mu g/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.

O efeito protetor do bicarbonato de sódio na nefropatia induzida por contraste radiológico em ratos

Contrastes radiológicos iodados – CI são causa de lesão renal aguda – LRA. Avaliar o efeito renoprotetor do bicarbonato de sódio (Bic) sobre a função renal (clearance de creatinina, Jaff é, Clcr-ml/min/100g) e o perfi l oxidativo (excreção de peróxidos, PU e de malondealdeído urinários, FOX-2 e TBARs, nmol/mgCr ) em ratos com CI. Ratos machos adultos Wistar, 250-300g, tratados 1x/dia, por 5 dias, foram divididos nos grupos: Salina (solução salina 0,9%, 3ml/kg/dia, intraperitoneal-i.p.); CI (ioxitalamato de meglumina e sódio, 3ml/kg, i.p); Bic+Salina (Bic 3ml/kg, i.p, 1 hora antes e 1 hora depois da Salina); Bic+CI (Bic 3ml/ kg, i.p, 1 hora antes e 1 hora depois do CI). CI induziu LRA e o Bic confi rmou seu efeito renoprotetor antioxidante (Clcr/TBARs/PU Salina: 0,59±0,03/0,11±0,02/1,29±0,24 vs Bic+Salina 0,58±0,03/0,13±0,02/1,32±0,64 vs CI 0,22±0,02A/0,19±0,02A/4,77±0, 24A vs Bic+CI 0,51±0,04B/0,13±0,3B/1,80± 0,04B, A/B p<0,05). O Bic confi rmou efeito protetor na LRA por CI, podendo ser considerado como possibilidade terapêutica para pacientes submetidos a CI.