The renoprotective effect of curcumin against cisplatin-induced acute kidney injury in mice: involvement of miR-181a/PTEN axis

Autor: Yanxiang Zhang, Ying Xiang, Si-Jia Huang, Quan Gong, Jing Huang, Yu Liu, Zhijiang Xi, Yun-Bo Yan, Jiao Qiu, Li Guan, Rui-Qiao Tan, Qing Tian, Shuai-Shuai Niu
Rok vydání: 2020
Předmět:
Male
PTEN
Curcumin
030232 urology & nephrology
cisplatin
Apoptosis
miR-181a
030204 cardiovascular system & hematology
Pharmacology
lcsh:RC870-923
Kidney
urologic and male genital diseases
Critical Care and Intensive Care Medicine
Blood Urea Nitrogen
Nephrotoxicity
Mice
03 medical and health sciences
chemistry.chemical_compound
AKI
0302 clinical medicine
Laboratory Study
Animals
Medicine
Cisplatin
biology
urogenital system
business.industry
Anti-Inflammatory Agents
Non-Steroidal
PTEN Phosphohydrolase
Acute kidney injury
General Medicine
Acute Kidney Injury
lcsh:Diseases of the genitourinary system. Urology
medicine.disease
female genital diseases and pregnancy complications
Mice
Inbred C57BL
MicroRNAs
Gene Expression Regulation
chemistry
Nephrology
Toxicity
biology.protein
business
renoprotective
medicine.drug
Zdroj: Renal Failure
Renal Failure, Vol 42, Iss 1, Pp 350-357 (2020)
ISSN: 1525-6049
0886-022X
DOI: 10.1080/0886022x.2020.1751658
Popis: Background: Nephrotoxicity, especially acute kidney injury (AKI), is the main dose-limiting toxicity of cisplatin. Although recent studies showed that curcumin prevented cisplatin-induced AKI effectively, further studies to understand the mechanism are required. Methods: We established an AKI mouse model. Male C57BL/6 mice were assigned to three groups: saline group (control), cisplatin group (CP), and curcumin + cisplatin group (CP + Cur). The CP group received a single intraperitoneal (i.p.) injection of cisplatin, while the control group received saline. The CP + Cur group received i.p. curcumin three days before cisplatin injection and curcumin administered for another three days until the day before euthanization. Renal injury was assessed by serological and histological analysis. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the phosphatase and tensin homolog (PTEN), and microRNA (miR)-181a expression in the renal tissues. Bioinformatics prediction and western blotting methods validated the targets of miR-181a in vitro. Results: Curcumin treatment alleviated cisplatin-induced nephrotoxicity as validated by the blood urea nitrogen (BUN) values, and histological analysis of kidneys. At the molecular level, curcumin treatment decreased miR-181a expression level, which was induced by cisplatin and restored the in vivo expression of PTEN, which was suppressed by cisplatin. We verified the direct regulation of PTEN by miR-181a in cultured human embryonic kidney 293T cells. Conclusions: We showed the involvement of miR-181a/PTEN axis in the renoprotective effect of curcumin against cisplatin-induced AKI, and provide new evidence on the ability of curcumin to alleviate cisplatin-induced nephrotoxicity.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje