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.
Highlights
Gadolinium-chelate (Gd) agents are used because of its paramagnetic properties that increases the quality of images in magnetic resonance imaging (MRI) [1]
Our results demonstrate that nephrectomized 5/6 (Nx) animals submitted to a single injection of gadolinium, showed 48 hours after contrast administration, a significant decrease in GFR and increased proteinuria rate, when compared with the 5/6 Nx rats which did not receive Gd chelate
We observed in nephrectomized rats that received gadolinium (Nx + Gd) significant changes in the parameters of iron metabolism, ferritin, transferrin saturation and a decrease in total iron binding capacity (TIBC) compared to nephrectomized rats (Nx) with statistical significance
Summary
Gadolinium-chelate (Gd) agents are used because of its paramagnetic properties that increases the quality of images in magnetic resonance imaging (MRI) [1]. The compounds are water soluble, excreted unchanged by glomerular filtration, do not suffer biotransformation and have good distribution in the extracellular fluid with a rapid equilibrium between the intravascular and interstitial compartments. Notable exceptions to these rules include gadoxetic acid and gadofosveset trisodium. Gadoxetic acid is taken up by hepatocytes; up to 50% of the agent is excreted in feces and 50% in urine. Between 80–96% of circulating gadofosveset trisodium is bound to plasma proteins, and the compound has been used as a blood pool agent [2]
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