Alpha-mangostin attenuates focal segmental glomerulosclerosis of mice induced by adriamycin.
10.11817/j.issn.1672-7347.2018.10.008
- Author:
Guoyong LIU
1
;
Lingling TANG
1
;
Jian SHE
1
;
Jiasi XU
1
;
Yanying GU
2
;
Hong LIU
3
,
4
;
Liyu HE
3
,
4
Author Information
1. Department of Nephrology, First Affiliated Hospital of Changde Vocational Technical College, Changde Hunan 415000, China.
2. Department of Infectious Disease, First Affiliated Hospital of Changde Vocational Technical College, Changde Hunan 415000, China.
3. Department of Nephrology, Second Xiangya Hospital, Central South University
4. Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha 410011, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Disease Models, Animal;
Doxorubicin;
Glomerulosclerosis, Focal Segmental;
chemically induced;
Kidney;
drug effects;
Mice;
Mice, Inbred NOD;
Protein Kinase Inhibitors;
pharmacology;
therapeutic use;
Xanthones;
pharmacology;
therapeutic use
- From:
Journal of Central South University(Medical Sciences)
2018;43(10):1089-1096
- CountryChina
- Language:Chinese
-
Abstract:
To observe the protective effect of alpha-mangostin (α-MG) on focal segmental glomurular sclerosis (FSGS) induced by adriamycin.
Methods: Adriamycin nephropathy (AN) model was induced by adriamycin (10 mg/kg) via a tail vein. Then the mice were treated with α-MG (12.5 mg/kg) or normal salin once daily for 6 weeks. At the end of 6 weeks, the mice were sacrificed, and the kidneys and blood samples were collected. Histopathology of the kidneys were analyzed under the optical microscope. The serum levels of biochemical indicators, such as serum creatinine (SCr), blood urea nitrogen (BUN) and cholesterol were determined. The levels of superoxide anion, malondialdehyde (MDA), and glutathione (GSH), the activity of superoxide dismutase (SOD) and catalase (CAT) in kidney tissues were determined. Serum levels of IL-1β, IL-18, IL-10 and adiponectin were determined. The levels of TGF-β1, collagen I (Col I), α-SMA, silent information regulator 1 (Sirt1) and the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) in kidney tissues were determined using immunohistochemical staining, Western blot, and RT-PCR.
Results: The levels of SCr, proteinuria, urine protein to creatinine ratio and serum cholesterol were attenuated in AN mice after α-MG treatment, while creatinine clearance rate and serum albumin were upregulated (P<0.05). α-MG treatment alleviated the glomerular and interstitial fibrosis, downregulated the expression of fibrosis markers, such as Col I and α-SMA (P<0.05). α-MG treatment reduced the production of superoxide anion, the levels of MDA and GSH, and increased the activity of CAT and SOD (P<0.05). α-MG treatment inhibitd the generation of pro-inflammatory cytokines, such as IL-1β and IL-18 and promoted the production of anti-inflammatory cytokines, such as the IL-10 and adiponectin (P<0.05); α-MG treatment promoted the expression of Sirt1, inhibitd the expression of NLRP3 in kidney tissues (P<0.05).
Conclusion: α-MG could attenuates FSGS of mice induced by adriamycin ameliorate and improve renal function. α-MG exerts its anti-inflammatory and anti-oxidative effects by up-regulation the expression of Sirt1 and suppression of NLRP3.
