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Arsenic and Selenium Profile in Erythrocytes of Renal Transplant Recipients.

ABSTRACT: Arsenic and selenium elements play extremely important roles in organisms. Too high As concentration in blood may lead to functional disorders within organs, including cancer. Arsenic is designated as a Group 1 human carcinogen by the International Agency for Research on Cancer that has established causal role of arsenic in cancers of the urinary bladder, lung, and skin in humans. In contrast, Se is believed to be the antioxidant trace element that is important in the biological defense against oxidative damage. We tested the hypothesis that immunosuppressive treatment based on mycophenolate mofetil (MMF), that is one of the most commonly used drug by renal transplant recipients, affects arsenic and selenium concentration in erythrocytes of renal transplant recipients. Current research was undertaken due to the fact that there are few studies on the concentration of chemical elements in the erythrocytes in kidney patients receiving immunosuppressive drugs. Monitoring of the concentration of chemical elements in the blood in patients who underwent kidney transplantation could be helpful, since chemical elements play an important role in many biological processes and it seems to be crucial in the prevention of cancer to which renal transplant recipients are more often exposed.The material consisted of blood from 115 renal transplant recipients of the Department of Nephrology, Transplantology, and Internal Medicine of Independent Public Clinical Hospital No. 2, Pomeranian Medical University, in the city of Szczecin in northwestern Poland. Arsenic and selenium levels in erythrocytes were quantified by inductively coupled mass spectroscopy.Men MMF+ had significantly higher As concentration than men MMF-. Se concentration was significantly higher in younger patients compared with older patients. The patients with lower creatinine level who used MMF had significantly higher As than MMF- patients. Patients whose therapy was based on MMF, cyclosporine A and glucocorticosteroids exhibited significantly higher concentration of As compared with patients whose regimen was based on MMF, tacrolimus, and glucocorticosteroids.This is the first study that demonstrates that regimen based on mycophenolate mofetil affects As and Se concentrations in erythrocytes in renal transplant recipients.

SUBMITTER: Wilk A

PROVIDER: S-EPMC7423803 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Arsenic and Selenium Profile in Erythrocytes of Renal Transplant Recipients.

Wilk Aleksandra A Wiszniewska Barbara B

Biological trace element research 20191223 2

Arsenic and selenium elements play extremely important roles in organisms. Too high As concentration in blood may lead to functional disorders within organs, including cancer. Arsenic is designated as a Group 1 human carcinogen by the International Agency for Research on Cancer that has established causal role of arsenic in cancers of the urinary bladder, lung, and skin in humans. In contrast, Se is believed to be the antioxidant trace element that is important in the biological defense against ...[more]

PMID: 31867677

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Project description:Mycophenolic acid (MPA), an immunosuppressive drug widely used in kidney transplantation, has been suggested to have anti-fibrotic effects. To analyze at a genomic level these effects, we prospectively studied a group of stable kidney transplant recipients (n=35) on cyclosporine (CyA) and azathioprine treatment. Twenty patients were converted from azathioprine to MPA (MPA group) and 15 patients continued on azathioprine (AZA group). RNA was extracted by peripheral blood mononuclear cells at baseline and 3 months thereafter. Genomic analysis, performed on 5 randomly-selected MPA patients, revealed that 17 genes discriminated the transcriptomic profile after conversion. Neutral endopeptidase (NEP), an enzyme degrading angiotensin-II, was the most significant up-regulated gene. NEP expression level was inversely correlated to proteinuria at baseline and after conversion. Immunohistochemistry on graft biopsy of 33 independent patients demonstrated higher glomerular and tubular NEP protein expression in CyA+MPA (n=13) compared to CyA+AZA (n=12) and CyA alone (n=8). Glomerular NEP levels were inversely correlated to proteinuria and glomerulosclerosis. Tubular NEP expression was inversely correlated to interstitial fibrosis. Incubation of proximal tubular cells with MPA led to a dose- and time-dependent increase of NEP gene expression. The direct influence of MPA on NEP expression may suggest a novel therapeutic effect of this drug. For microarray analysis, we studied 5 randomly selected patients included in the training group. Patients included in this group were, at the time of enrollment (T0), on standard maintenance immunosuppression with Cyclosporine (Neoral, Novartis, Basel, mean±SD of daily dose: 160.1±37.1mg), prednisone (5 mg daily) and Azathioprine (50 mg daily). Twenty patients, at T0, were switched from Azathioprine to EC-MPS (Myfortic, Novartis, Basel, 720 mg bid) for their need of allopurinol therapy (EC-MPS group). However, to avoid confounding factors, allopurinol treatment did not start until the end of our study (3 months). For the microarray analysis, we randomly selected 5 patients from the EC-MPS group. PBMC both at T0 and at T1 (3 months after the switching of the therapy) were immediately isolated from 20 ml of whole blood by Ficoll–Hypaque (Flow Laboratories, Irvine, UK) density gradient centrifugation. Total RNA was extracted by RNeasy mini kit (QIAGEN Inc., Valencia, CA) according the manufacturer’s instructions. Total RNA was processed and hybridized to the Affymetrix GeneChips Human Genome U133 Array Set HG-U133A (Affymetrix)(Affymetrix, Santa Clara, CA)

Dataset Information

Arsenic and Selenium Profile in Erythrocytes of Renal Transplant Recipients.

Publications

Arsenic and Selenium Profile in Erythrocytes of Renal Transplant Recipients.

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