Abstract

Oxidative stress is exacerbated in hemodialysis patients by several factors, including the uremic environment and the use of dialysis fluids (DFs). Since magnesium (Mg) plays a key role in modulating immune function and in reducing oxidative stress, we aimed to evaluate whether increasing the Mg concentration in different DFs could protect against oxidative stress in immunocompetent cells in vitro. Effect of ADF (acetate 3 mM), CDF (citrate 1 mM), and ACDF (citrate 0.8 mM + acetate 0.3 mM) dialysates with Mg at standard (0.5 mM) or higher (1, 1.25, and 2 mM) concentrations were assessed in THP-1 monocyte cultures. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels were quantified under basal and uremic conditions (indoxyl sulfate (IS) treatment). Under uremic conditions, the three DFs with 0.5 mM Mg promoted higher ROS production and lipid damage than the control solution. However, CDF and ACDF induced lower levels of ROS and MDA, compared to that induced by ADF. High Mg concentration (1.25 and/or 2 mM) in CDF and ACDF protected against oxidative stress, indicated by reduced ROS and MDA levels compared to respective DFs with standard concentration of Mg. Increasing Mg concentrations in ADF promoted high ROS production and MDA content. Thus, an increase in Mg content in DFs has differential effects on the oxidative stress in IS-treated THP-1 cells depending on the dialysate used.

Highlights

  • Chronic kidney disease (CKD) patients have a high incidence of cardiovascular disease (CVD), which remains the leading cause of morbimortality in hemodialysis (HD) patients [1,2,3]

  • THP-1 monocytes were grown in the presence of three different dialysis fluids (DFs) (ADF, ACDF, and CDF) with similar standard Mg concentrations (0.5 mM)

  • Since high reactive oxygen species (ROS) levels could promote oxidative damage, we investigated whether the supplementation of ADF, ACDF, and CDF with high doses of Mg (1, 1.25, and 2 mM) could prevent oxidative lipid damage in THP-1 monocytes cultured under basal or indoxyl sulfate (IS)-stimulated conditions

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Summary

Introduction

Chronic kidney disease (CKD) patients have a high incidence of cardiovascular disease (CVD), which remains the leading cause of morbimortality in hemodialysis (HD) patients [1,2,3]. Several factors are closely associated with the pathophysiology of both CKD and CVD [3]. UTs are divided into three categories: low-molecular-weight water-soluble solutes (500 Da), and protein-bound solutes [8]. These uremic toxins, represented by IS, is extremely toxic and difficult to eliminate by conventional dialysis; high IS levels may trigger oxidative-inflammatory stress, playing a key pathophysiologic role in CKD. Several studies have confirmed that the occurrence of CVD induced by CKD is closely related to the IS accumulation [3]

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