Enhanced Oxidative DNA-Damage in Peritoneal Dialysis Patients via the TXNIP/TRX Axis

Peritoneal dialysis (PD) is an effective method of renal replacement therapy, providing a high level of patient autonomy. Nevertheless, the long-term use of PD is limited due to deleterious effects of PD fluids to the structure and function of the peritoneal membrane leading to loss of dialysis effi...

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Bibliographic Details
Published in:Antioxidants 2022-06, Vol.11 (6), p.1124
Main Authors: Oberacker, Tina, Fritz, Peter, Schanz, Moritz, Alscher, Mark Dominik, Ketteler, Markus, Schricker, Severin
Format: Article
Language:English
Subjects:
Adipocytes
Autonomy
Biopsy
Catheters
Deoxyribonucleic acid
Diabetes
DNA
DNA damage
Enzyme-linked immunosorbent assay
Enzymes
Glucose
Homeostasis
Hypertension
Immunohistochemistry
Kidney diseases
Membrane proteins
Ostomy
oxidative damage
Oxidative stress
Patients
Peritoneal dialysis
Peritoneum
Plasma
Proteins
Structure-function relationships
Thioredoxin
thioredoxin-interacting-protein
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Summary:Peritoneal dialysis (PD) is an effective method of renal replacement therapy, providing a high level of patient autonomy. Nevertheless, the long-term use of PD is limited due to deleterious effects of PD fluids to the structure and function of the peritoneal membrane leading to loss of dialysis efficacy. PD patients show excessive oxidative stress compared to controls or chronic kidney disease (CKD) patients not on dialysis. Therefore, defense systems against detrimental events play a pivotal role in the integrity of the peritoneal membrane. The thioredoxin-interacting-protein (TXNIP)/thioredoxin (TRX) system also plays a major role in maintaining the redox homeostasis. We hypothesized that the upregulation of TXNIP negatively influences TRX activity, resulting in enhanced oxidative DNA-damage in PD patients. Therefore, we collected plasma samples and human peritoneal biopsies of healthy controls and PD patients as well. Using ELISA-analysis and immunohistochemistry, we showed that PD patients had elevated TXNIP levels compared to healthy controls. Furthermore, we demonstrated that PD patients had a reduced TRX activity, thereby leading to increased oxidative DNA-damage. Hence, targeting the TXNIP/TRX system as well as the use of oxidative stress scavengers could become promising therapeutic approaches potentially applicable in clinical practice in order to sustain and improve peritoneal membrane function.
ISSN:2076-3921
2076-3921
DOI:10.3390/antiox11061124