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Title: Effect of quercetin on metallothionein, nitric oxide synthases and cyclooxygenase-2 expression on experimental chronic cadmium nephrotoxicity in rats

Abstract

Inflammation can play a key role in Cd-induced dysfunctions. Quercetin is a potent oxygen free radical scavenger and a metal chelator. Our aim was to study the effect of quercetin on Cd-induced kidney damage and metallothionein expression. The study was performed in Wistar rats that were administered during 9 weeks with either cadmium (1.2 mg Cd/kg/day, s.c.), quercetin (50 mg/kg/day, i.p.) or cadmium + quercetin. Renal toxicity was evaluated by measuring blood urea nitrogen concentration and urinary excretion of enzymes marker of tubular damage. Endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) renal expression were assessed by Western blot. Renal expression of metallothionein 1 and 2 (MT-1, MT-2) and eNOS mRNA was assessed by Northern blot. Our data demonstrated that Cd-induced renal toxicity was markedly reduced in rats that also received quercetin. MT-1 and MT-2 mRNA levels in kidney were substantially increased during treatment with Cd, being even higher when the animals received Cd and quercetin. Renal eNOS expression was significantly higher in rats receiving Cd and quercetin than in animals receiving Cd alone or in control rats. In the group that received Cd, COX-2 and iNOS expression was markedly higher than in control rats.more » In the group Cd + quercetin, no changes in COX-2 and iNOS expression were observed compared with the control group. Our results demonstrate that quercetin treatment prevents Cd-induced overexpression of iNOS and COX-2, and increases MT expression. These effects can explain the protection by quercetin of Cd-induced nephrotoxicity.« less

Authors:
 [1];  [1];  [1];  [2];  [1];  [1];  [3]
  1. Instituto Reina Sofia de Investigacion Nefrologica, Departamento de Fisiologia y Farmacologia, Edificio Departamental, Campus Miguel de Unamuno, 37007 Salamanca (Spain)
  2. Departamento de Bioquimica Clinica, Hospital Universitario de Salamanca, Salamanca (Spain)
  3. Instituto Reina Sofia de Investigacion Nefrologica, Departamento de Fisiologia y Farmacologia, Edificio Departamental, Campus Miguel de Unamuno, 37007 Salamanca (Spain). E-mail: jmlnovoa@usal.es
Publication Date:
OSTI Identifier:
20783410
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 210; Journal Issue: 1-2; Other Information: DOI: 10.1016/j.taap.2005.09.006; PII: S0041-008X(05)00561-2; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIOXIDANTS; BLOOD; CADMIUM; CARBON MONOXIDE; DAMAGE; EXCRETION; INDIUM OXIDES; INFLAMMATION; KIDNEYS; METALLOTHIONEIN; NITRIC OXIDE; QUERCETIN; RATS; TOXICITY; UREA

Citation Formats

Morales, Ana I., Vicente-Sanchez, Cesar, Jerkic, Mirjana, Santiago, Jose M., Sanchez-Gonzalez, Penelope D., Perez-Barriocanal, Fernando, and Lopez-Novoa, Jose M. Effect of quercetin on metallothionein, nitric oxide synthases and cyclooxygenase-2 expression on experimental chronic cadmium nephrotoxicity in rats. United States: N. p., 2006. Web. doi:10.1016/j.taap.2005.09.006.
Morales, Ana I., Vicente-Sanchez, Cesar, Jerkic, Mirjana, Santiago, Jose M., Sanchez-Gonzalez, Penelope D., Perez-Barriocanal, Fernando, & Lopez-Novoa, Jose M. Effect of quercetin on metallothionein, nitric oxide synthases and cyclooxygenase-2 expression on experimental chronic cadmium nephrotoxicity in rats. United States. doi:10.1016/j.taap.2005.09.006.
Morales, Ana I., Vicente-Sanchez, Cesar, Jerkic, Mirjana, Santiago, Jose M., Sanchez-Gonzalez, Penelope D., Perez-Barriocanal, Fernando, and Lopez-Novoa, Jose M. Sun . "Effect of quercetin on metallothionein, nitric oxide synthases and cyclooxygenase-2 expression on experimental chronic cadmium nephrotoxicity in rats". United States. doi:10.1016/j.taap.2005.09.006.
@article{osti_20783410,
title = {Effect of quercetin on metallothionein, nitric oxide synthases and cyclooxygenase-2 expression on experimental chronic cadmium nephrotoxicity in rats},
author = {Morales, Ana I. and Vicente-Sanchez, Cesar and Jerkic, Mirjana and Santiago, Jose M. and Sanchez-Gonzalez, Penelope D. and Perez-Barriocanal, Fernando and Lopez-Novoa, Jose M.},
abstractNote = {Inflammation can play a key role in Cd-induced dysfunctions. Quercetin is a potent oxygen free radical scavenger and a metal chelator. Our aim was to study the effect of quercetin on Cd-induced kidney damage and metallothionein expression. The study was performed in Wistar rats that were administered during 9 weeks with either cadmium (1.2 mg Cd/kg/day, s.c.), quercetin (50 mg/kg/day, i.p.) or cadmium + quercetin. Renal toxicity was evaluated by measuring blood urea nitrogen concentration and urinary excretion of enzymes marker of tubular damage. Endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) renal expression were assessed by Western blot. Renal expression of metallothionein 1 and 2 (MT-1, MT-2) and eNOS mRNA was assessed by Northern blot. Our data demonstrated that Cd-induced renal toxicity was markedly reduced in rats that also received quercetin. MT-1 and MT-2 mRNA levels in kidney were substantially increased during treatment with Cd, being even higher when the animals received Cd and quercetin. Renal eNOS expression was significantly higher in rats receiving Cd and quercetin than in animals receiving Cd alone or in control rats. In the group that received Cd, COX-2 and iNOS expression was markedly higher than in control rats. In the group Cd + quercetin, no changes in COX-2 and iNOS expression were observed compared with the control group. Our results demonstrate that quercetin treatment prevents Cd-induced overexpression of iNOS and COX-2, and increases MT expression. These effects can explain the protection by quercetin of Cd-induced nephrotoxicity.},
doi = {10.1016/j.taap.2005.09.006},
journal = {Toxicology and Applied Pharmacology},
number = 1-2,
volume = 210,
place = {United States},
year = {Sun Jan 15 00:00:00 EST 2006},
month = {Sun Jan 15 00:00:00 EST 2006}
}