Diverse Effect of Vitamin C and N-Acetylcysteine on Aluminum-Induced Eryptosis

Purpose. The role of oxidative stress in Aluminum (Al)-induced apoptotic effects has been investigated and suicidal death of erythrocytes, eryptosis, is characterized by cell shrinkage and phosphatidylserine externalization (PSE) at the surface of the erythrocyte cell membrane. Eryptosis is stimulat...

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Main Authors: Ali Reza Zangeneh, Mohammad Ali Takhshid, Reza Ranjbaran, Mahsa Maleknia, Mohammad Hassan Meshkibaf
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Biochemistry Research International
Online Access:http://dx.doi.org/10.1155/2021/6670656
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author Ali Reza Zangeneh
Mohammad Ali Takhshid
Reza Ranjbaran
Mahsa Maleknia
Mohammad Hassan Meshkibaf
author_facet Ali Reza Zangeneh
Mohammad Ali Takhshid
Reza Ranjbaran
Mahsa Maleknia
Mohammad Hassan Meshkibaf
author_sort Ali Reza Zangeneh
collection DOAJ
description Purpose. The role of oxidative stress in Aluminum (Al)-induced apoptotic effects has been investigated and suicidal death of erythrocytes, eryptosis, is characterized by cell shrinkage and phosphatidylserine externalization (PSE) at the surface of the erythrocyte cell membrane. Eryptosis is stimulated by an increase in cytosolic Ca2+ concentration and reactive oxygen species (ROS). This ex vivo study was conducted to evaluate the effect of well-known antioxidants including vitamin C (vit C) and N-acetylcysteine (NAC), against Al-induced hemolysis and eryptosis. Methods. Isolated erythrocytes from the healthy volunteers were partitioned into various groups (6 replicates/group) and treated by various concentrations of Al (3–100 µM) in the presence and absence of vit C (0.6 mM) and NAC (1 mM). After 24 hours of treatment, hemolysis was determined from hemoglobin levels in the supernatant. Flowcytometric methods were applied to measure PSE, cell shrinkage, Ca2+ content, and ROS abundance using annexin V-binding, forward scatter, Fluo3-fluorescence, and DCFDA dependent fluorescence, respectively. Reduced glutathione (GSH) was measured by the ELISA method. Results. The results showed that a 24 hours’ exposure of the erythrocytes to Al (10–100 µM) significantly increased hemolysis in a dose and Ca2+dependent manner. Al also dramatically decreased forward scatter. The percentage of PSE cells, Fluo3-fluorescence, and DCFDA fluorescence were increased by Al. Furthermore, cotreatment with NAC inhibited the effect of Al on hemolysis, eryptosis, and ROS production. Vit C decreased Al-induced ROS production. However, increased Al-induced eryptosis. There were no significant changes in glutathione after the ALCL3 treatment. Conclusions. Al-induced eryptosis and hemolysis through triggering oxidative stress, while NAC could diverse this effect. In contrast, vit C might intensify Al-induced eryptosis at particular doses through a less known mechanism.
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spelling doaj-art-85d7d15b4c924dddb03355d8225abd2f2025-08-20T03:38:03ZengWileyBiochemistry Research International2090-22472090-22552021-01-01202110.1155/2021/66706566670656Diverse Effect of Vitamin C and N-Acetylcysteine on Aluminum-Induced EryptosisAli Reza Zangeneh0Mohammad Ali Takhshid1Reza Ranjbaran2Mahsa Maleknia3Mohammad Hassan Meshkibaf4Department of Clinical Biochemistry, Fasa University of Medical Sciences, Fasa, IranDiagnostic Laboratory Sciences and Technology Research Center, Faculty of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, IranDiagnostic Laboratory Sciences and Technology Research Center, Faculty of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, IranDepartment of Clinical Biochemistry, Fasa University of Medical Sciences, Fasa, IranDepartment of Clinical Biochemistry, Fasa University of Medical Sciences, Fasa, IranPurpose. The role of oxidative stress in Aluminum (Al)-induced apoptotic effects has been investigated and suicidal death of erythrocytes, eryptosis, is characterized by cell shrinkage and phosphatidylserine externalization (PSE) at the surface of the erythrocyte cell membrane. Eryptosis is stimulated by an increase in cytosolic Ca2+ concentration and reactive oxygen species (ROS). This ex vivo study was conducted to evaluate the effect of well-known antioxidants including vitamin C (vit C) and N-acetylcysteine (NAC), against Al-induced hemolysis and eryptosis. Methods. Isolated erythrocytes from the healthy volunteers were partitioned into various groups (6 replicates/group) and treated by various concentrations of Al (3–100 µM) in the presence and absence of vit C (0.6 mM) and NAC (1 mM). After 24 hours of treatment, hemolysis was determined from hemoglobin levels in the supernatant. Flowcytometric methods were applied to measure PSE, cell shrinkage, Ca2+ content, and ROS abundance using annexin V-binding, forward scatter, Fluo3-fluorescence, and DCFDA dependent fluorescence, respectively. Reduced glutathione (GSH) was measured by the ELISA method. Results. The results showed that a 24 hours’ exposure of the erythrocytes to Al (10–100 µM) significantly increased hemolysis in a dose and Ca2+dependent manner. Al also dramatically decreased forward scatter. The percentage of PSE cells, Fluo3-fluorescence, and DCFDA fluorescence were increased by Al. Furthermore, cotreatment with NAC inhibited the effect of Al on hemolysis, eryptosis, and ROS production. Vit C decreased Al-induced ROS production. However, increased Al-induced eryptosis. There were no significant changes in glutathione after the ALCL3 treatment. Conclusions. Al-induced eryptosis and hemolysis through triggering oxidative stress, while NAC could diverse this effect. In contrast, vit C might intensify Al-induced eryptosis at particular doses through a less known mechanism.http://dx.doi.org/10.1155/2021/6670656
spellingShingle Ali Reza Zangeneh
Mohammad Ali Takhshid
Reza Ranjbaran
Mahsa Maleknia
Mohammad Hassan Meshkibaf
Diverse Effect of Vitamin C and N-Acetylcysteine on Aluminum-Induced Eryptosis
Biochemistry Research International
title Diverse Effect of Vitamin C and N-Acetylcysteine on Aluminum-Induced Eryptosis
title_full Diverse Effect of Vitamin C and N-Acetylcysteine on Aluminum-Induced Eryptosis
title_fullStr Diverse Effect of Vitamin C and N-Acetylcysteine on Aluminum-Induced Eryptosis
title_full_unstemmed Diverse Effect of Vitamin C and N-Acetylcysteine on Aluminum-Induced Eryptosis
title_short Diverse Effect of Vitamin C and N-Acetylcysteine on Aluminum-Induced Eryptosis
title_sort diverse effect of vitamin c and n acetylcysteine on aluminum induced eryptosis
url http://dx.doi.org/10.1155/2021/6670656
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AT mahsamaleknia diverseeffectofvitamincandnacetylcysteineonaluminuminducederyptosis
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