%0 Journal Article
%T Effect of Indoxyl Sulfate on Oxidative Stress, Apoptosis, and Monocyte Chemoattractant Protein-1 in Leukocytes
%A Edgar Ferreira da Cruz
%A Miguel Cendoroglo
%A Silvia Regina Manfredi
%A Maria Eug那nia Canziani
%A Beata Marie Redublo Quinto
%A Caren Cristina Grabulosa
%A Nadia Karina Guimarˋes-Souza
%A Aline Trevisan Peres
%A Jos谷 Tarc赤sio Giffoni de Carvalho
%A Marcelo Costa Batista
%A Maria Aparecida Dalboni
%J ISRN Oxidative Medicine
%D 2014
%R 10.1155/2014/412389
%X This study showed that indoxyl sulfate, an uremic toxin present in the serum of patients with chronic kidney disease, increases oxidative stress and apoptosis in human neutrophils and reduces the production of monocyte chemoattractant protein-1 (MCP-1) by peripheral blood mononuclear cell (PBMC). It is possible that these effects caused by this toxin contribute to vascular injury of the endothelium and decreased response to infectious insults, respectively. 1. Introduction Uremic toxins are solutes that accumulate in the plasma of patients with loss of renal function [1每4]. More than 100 uremic solutes and toxins have been classified by the ※European Uremic Toxin Work Group§ (EUTox) [5, 6]. Uremic toxins have been considered one of the main factors that contribute to the state of inflammation [7每9] and have been associated with immune dysfunction in patients with chronic kidney disease (CKD) [10每17]. They have also been associated with cardiovascular disease (CVD), particularly because of their effects on different cells types leading to the generation of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2), hydroxyl radical (OH-), and superoxide anion ( ) [18, 19] that contribute to oxidization of lipids, protein, and DNA damage. In addition, uremic plasma induces synthesis of inflammatory mediators as IL-1 [20], IL-6 [20], IL-12 [21], TNF- [22], and IL-10 [23] and chemokine as IL-8 [22] and Monocyte chemoattractant protein-1 (MCP-1) [24, 25]. MCP-1 is one of the key chemokines that regulate migration and infiltration of monocytes/macrophages and it has been demonstrated to be induced and involved in various diseases. Migration of monocytes from the blood stream across the vascular endothelium is required for routine immunological surveillance of tissues, as well as in response to inflammation. Besides, MCP-1 is produced by a variety of cell types, either constitutively or after induction by toxins, oxidative stress, cytokines, or growth factors. The immunosuppression observed in patients with CKD has also been associated with uremic toxins that contribute to dysregulated apoptosis of leukocytes and other cell types [9, 26每28]. The uremic toxin indoxyl sulfate (IS) has been associated with inflammation and renal interstitial fibrosis and both processes contribute to progression of CKD [26]. This toxin originates from the intestinal metabolism of tryptophan, which is metabolized into indole by the action of tryptophanase produced by bacteria such as Escherichia coli present in the intestinal microbiota. The newly synthesized indole is absorbed
%U http://www.hindawi.com/journals/isrn.oxidative.medicine/2014/412389/