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Cyclophilin D Promotes Acute, but Not Chronic, Kidney Injury in a Mouse Model of Aristolochic Acid Toxicity
- Source :
- Toxins, Toxins, Vol 13, Iss 700, p 700 (2021), Volume 13, Issue 10
- Publication Year :
- 2021
-
Abstract
- The plant-derived toxin, aristolochic acid (AA), is the cause of Chinese Herb Nephropathy and Balkan Nephropathy. Ingestion of high dose AA induces acute kidney injury, while chronic low dose ingestion leads to progressive kidney disease. Ingested AA is taken up by tubular epithelial cells of the kidney, leading to DNA damage and cell death. Cyclophilin D (CypD) participates in mitochondrial-dependent cell death, but whether this mechanism operates in acute or chronic AA-induced kidney injury is unknown. We addressed this question by exposing CypD-/- and wild type (WT) mice to acute high dose, or chronic low dose, AA. Administration of 5 mg/kg AA to WT mice induced acute kidney injury 3 days later, characterised by loss of kidney function, tubular cell damage and death, and neutrophil infiltration. All of these parameters were significantly reduced in CypD-/- mice. Chronic low dose (2 mg/kg AA) administration in WT mice resulted in chronic kidney disease with impaired renal function and renal fibrosis by day 28. However, CypD-/- mice were not protected from AA-induced chronic kidney disease. In conclusion, CypD facilitates AA-induced acute kidney damage, but CypD does not contribute to the transition of acute kidney injury to chronic kidney disease during ongoing AA exposure.
- Subjects :
- Health, Toxicology and Mutagenesis
aristolochic acid
Aristolochic acid
Renal function
Pharmacology
Toxicology
Article
Nephropathy
chemistry.chemical_compound
Mice
medicine
Renal fibrosis
Animals
Renal Insufficiency, Chronic
Kidney
business.industry
urogenital system
Acute kidney injury
Acute Kidney Injury
medicine.disease
renal fibrosis
Disease Models, Animal
medicine.anatomical_structure
cell death
chemistry
inflammation
Toxicity
Medicine
Aristolochic Acids
business
cyclophilin D
chronic kidney disease
Kidney disease
Subjects
Details
- ISSN :
- 20726651
- Volume :
- 13
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Toxins
- Accession number :
- edsair.doi.dedup.....e90c9efaf0970c481314996ebc41ca37