Silvia D Rodrigues1, Karime C França1, Fernando T Dallin1, Clarice K Fujihara2, Aguinaldo J Nascimento3, Roberto Pecoits-Filho4, Lia S Nakao5. 1. Departamento de Patologia Básica, Universidade Federal do Paraná, Centro Politécnico, Curitiba 81531-980, Brazil. 2. Laboratório de Fisiopatologia Renal, Faculdade de Medicina, Universidade de São Paulo, São Paulo 01246-903, Brazil. 3. Programa de Pós-Graduação em Ciências Farmacêuticas,Universidade Federal do Paraná, Curitiba 80210-170, Brazil. 4. School of Medicine, Pontifícia Universidade Católica do Paraná, Rua Imaculada Conceição 1155, Curitiba 80215-901, Brazil. 5. Departamento de Patologia Básica, Universidade Federal do Paraná, Centro Politécnico, Curitiba 81531-980, Brazil. Electronic address: lia.nakao@ufpr.br.
Abstract
AIMS: Chronic kidney disease (CKD) progression is accompanied by systemic oxidative stress, which contributes to an increase in the risk of cardiovascular diseases (CVDs). N-acetylcysteine (NAC) is among the most studied antioxidants, but its therapeutic benefits in CKD-associated CVDs remain controversial. Here, we investigated whether NAC could inhibit the oxidative stress induced by uremia in vitro and in vivo. MAIN METHODS: Endothelial and smooth muscle cells were challenged with human uremic or non-uremic sera, and the effects of a pre-treatment with 2mM NAC were evaluated. Reactive oxygen species (ROS) production, protein oxidation and total glutathione/glutathione disulfide (tGSH/GSSG) ratios were measured. Five-sixths nephrectomized or sham-operated rats were orally treated (in the drinking water) with 60 mg/kg/day NAC or not treated for 53 days. Plasma cysteine/cystine reduction potential Eh(Cyss/2Cys) was determined as a novel marker of the systemic oxidative stress. KEY FINDINGS: NAC inhibited all the determined oxidative stress parameters, likely by increasing the tGSH/GSSG ratio, in both cell lines exposed to uremic serum. Orally administered NAC attenuated the systemic oxidative stress in uremic rats. SIGNIFICANCE: The present results indicate that NAC, by preventing GSH depletion in vascular cells exposed to uremic serum and by attenuating the systemic oxidative stress during CKD progression, emerges as a potential strategy to prevent the oxidative stress induced by uremic toxicity in the vascular system.
AIMS: Chronic kidney disease (CKD) progression is accompanied by systemic oxidative stress, which contributes to an increase in the risk of cardiovascular diseases (CVDs). N-acetylcysteine (NAC) is among the most studied antioxidants, but its therapeutic benefits in CKD-associated CVDs remain controversial. Here, we investigated whether NAC could inhibit the oxidative stress induced by uremia in vitro and in vivo. MAIN METHODS: Endothelial and smooth muscle cells were challenged with human uremic or non-uremic sera, and the effects of a pre-treatment with 2mM NAC were evaluated. Reactive oxygen species (ROS) production, protein oxidation and total glutathione/glutathione disulfide (tGSH/GSSG) ratios were measured. Five-sixths nephrectomized or sham-operated rats were orally treated (in the drinking water) with 60 mg/kg/day NAC or not treated for 53 days. Plasma cysteine/cystine reduction potential Eh(Cyss/2Cys) was determined as a novel marker of the systemic oxidative stress. KEY FINDINGS:NAC inhibited all the determined oxidative stress parameters, likely by increasing the tGSH/GSSG ratio, in both cell lines exposed to uremic serum. Orally administered NAC attenuated the systemic oxidative stress in uremic rats. SIGNIFICANCE: The present results indicate that NAC, by preventing GSH depletion in vascular cells exposed to uremic serum and by attenuating the systemic oxidative stress during CKD progression, emerges as a potential strategy to prevent the oxidative stress induced by uremic toxicity in the vascular system.
Authors: Matthew R Allen; Joseph Wallace; Erin McNerney; Jeffry Nyman; Keith Avin; Neal Chen; Sharon Moe Journal: PLoS One Date: 2020-03-23 Impact factor: 3.240