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Kahweol Ameliorates Cisplatin-Induced Acute Kidney Injury through Pleiotropic Effects in Mice
- Source :
- Biomedicines, Vol 8, Iss 572, p 572 (2020), Biomedicines, Volume 8, Issue 12
- Publication Year :
- 2020
- Publisher :
- MDPI AG, 2020.
-
Abstract
- Cisplatin is an effective chemotherapeutic agent, but its clinical use is frequently limited by its nephrotoxicity. The pathogenesis of cisplatin-induced acute kidney injury (AKI) remains incompletely understood, but oxidative stress, tubular cell death, and inflammation are considered important contributors to cisplatin-induced renal injury. Kahweol is a natural diterpene extracted from coffee beans and has been shown to possess anti-oxidative and anti-inflammatory properties. However, its role in cisplatin-induced nephrotoxicity remains undetermined. Therefore, we investigated whether kahweol exerts a protective effect against cisplatin-induced renal injury. Additionally, its mechanisms were also examined. Administration of kahweol attenuated renal dysfunction and histopathological damage together with inhibition of oxidative stress in cisplatin-injected mice. Increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and decreased expression of manganese superoxide dismutase and catalase after cisplatin treatment were significantly reversed by kahweol. Moreover, kahweol inhibited cisplatin-induced apoptosis and necroptosis in the kidneys. Finally, kahweol reduced inflammatory cytokine production and immune cell accumulation together with suppression of nuclear factor kappa-B pathway and downregulation of vascular adhesion molecules. Together, these results suggest that kahweol ameliorates cisplatin-induced renal injury via its pleiotropic effects and might be a potential preventive option against cisplatin-induced nephrotoxicity.
- Subjects :
- Necroptosis
coffee
necroptosis
Medicine (miscellaneous)
cisplatin
Inflammation
Pharmacology
medicine.disease_cause
Article
General Biochemistry, Genetics and Molecular Biology
Nephrotoxicity
kahweol
chemistry.chemical_compound
medicine
oxidative stress
lcsh:QH301-705.5
Kahweol
business.industry
Acute kidney injury
apoptosis
medicine.disease
chemistry
acute kidney injury
lcsh:Biology (General)
inflammation
Apoptosis
medicine.symptom
business
Nicotinamide adenine dinucleotide phosphate
Oxidative stress
Subjects
Details
- Language :
- English
- ISSN :
- 22279059
- Volume :
- 8
- Issue :
- 572
- Database :
- OpenAIRE
- Journal :
- Biomedicines
- Accession number :
- edsair.doi.dedup.....0a51c2c603694a9a6648ab5effeccc89