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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 - cycli...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397987/ https://www.ncbi.nlm.nih.gov/pubmed/22815709 http://dx.doi.org/10.1371/journal.pone.0039528 |
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author | Pereira, Leonardo Victor Barbosa Shimizu, Maria Heloisa Massola Rodrigues, Lina Paola Miranda Ruiz Leite, Cláudia Costa Andrade, Lúcia Seguro, Antonio Carlos |
author_facet | Pereira, Leonardo Victor Barbosa Shimizu, Maria Heloisa Massola Rodrigues, Lina Paola Miranda Ruiz Leite, Cláudia Costa Andrade, Lúcia Seguro, Antonio Carlos |
author_sort | Pereira, Leonardo Victor Barbosa |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3397987 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33979872012-07-19 N-Acetylcysteine Protects Rats with Chronic Renal Failure from Gadolinium-Chelate Nephrotoxicity Pereira, Leonardo Victor Barbosa Shimizu, Maria Heloisa Massola Rodrigues, Lina Paola Miranda Ruiz Leite, Cláudia Costa Andrade, Lúcia Seguro, Antonio Carlos PLoS One Research Article 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. Public Library of Science 2012-07-16 /pmc/articles/PMC3397987/ /pubmed/22815709 http://dx.doi.org/10.1371/journal.pone.0039528 Text en Pereira et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Pereira, Leonardo Victor Barbosa Shimizu, Maria Heloisa Massola Rodrigues, Lina Paola Miranda Ruiz Leite, Cláudia Costa Andrade, Lúcia Seguro, Antonio Carlos N-Acetylcysteine Protects Rats with Chronic Renal Failure from Gadolinium-Chelate Nephrotoxicity |
title | N-Acetylcysteine Protects Rats with Chronic Renal Failure from Gadolinium-Chelate Nephrotoxicity |
title_full | N-Acetylcysteine Protects Rats with Chronic Renal Failure from Gadolinium-Chelate Nephrotoxicity |
title_fullStr | N-Acetylcysteine Protects Rats with Chronic Renal Failure from Gadolinium-Chelate Nephrotoxicity |
title_full_unstemmed | N-Acetylcysteine Protects Rats with Chronic Renal Failure from Gadolinium-Chelate Nephrotoxicity |
title_short | N-Acetylcysteine Protects Rats with Chronic Renal Failure from Gadolinium-Chelate Nephrotoxicity |
title_sort | n-acetylcysteine protects rats with chronic renal failure from gadolinium-chelate nephrotoxicity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397987/ https://www.ncbi.nlm.nih.gov/pubmed/22815709 http://dx.doi.org/10.1371/journal.pone.0039528 |
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