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Inhibition of thioredoxin reductase 1 correlates with platinum-based chemotherapeutic induced tissue injury
- Source :
- Biochemical pharmacology. 175
- Publication Year :
- 2019
-
Abstract
- Platinum-containing drugs (PtDs; e.g. cisplatin, carboplatin, and oxaliplatin) have been widely used as anticancer reagents against various cancers. However, treatment with these drugs results in undesirable adverse effects with unknown mechanisms. Herein, we found a strong correlation between the inhibitory effects of PtDs on cytosolic thioredoxin reductase (TXNRD1) and tissue injury. Of the PtDs tested, cisplatin was found to be the most effective inhibitory PtD against TXRND1, causing the severest kidney injury. The initial inhibition of TXNRD1 in the kidney resulted from cisplatin-induced transcriptional activation of Nrf2-regulated genes including Txnrd1. However, the antioxidant responses in the kidney did not reverse the cisplatin-induced oxidation process. Nephrotoxicity was accompanied with an increase of protein glutathionylation and a cellular thiol redox environment oxidation. These results suggest that the changes of the cellular thiol-dependent redox environment regulated by TXNRD1 is a major event in the adverse effects of cisplatin in kidney.
- Subjects :
- 0301 basic medicine
Male
Thioredoxin Reductase 1
Thioredoxin reductase
Antineoplastic Agents
Pharmacology
Protein glutathionylation
medicine.disease_cause
Kidney
Biochemistry
Nephrotoxicity
Carboplatin
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
medicine
Animals
Cisplatin
Hydrogen Peroxide
Recombinant Proteins
Oxaliplatin
Mitochondria
Mice, Inbred C57BL
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
Oxidation-Reduction
Oxidative stress
medicine.drug
Subjects
Details
- ISSN :
- 18732968
- Volume :
- 175
- Database :
- OpenAIRE
- Journal :
- Biochemical pharmacology
- Accession number :
- edsair.doi.dedup.....2512fbd841c564d60f59ac29516d37dd