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Curcumin ameliorates peritoneal fibrosis via inhibition of transforming growth factor-activated kinase 1 (TAK1) pathway in a rat model of peritoneal dialysis.
- Source :
-
BMC complementary and alternative medicine [BMC Complement Altern Med] 2019 Oct 23; Vol. 19 (1), pp. 280. Date of Electronic Publication: 2019 Oct 23. - Publication Year :
- 2019
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Abstract
- Background: Peritoneal fibrosis (PF) remains a serious complication of long-term peritoneal dialysis (PD). The goal of this study was to investigate the anti-fibrotic effects of curcumin on the PF response to PD and its' mechanism.<br />Methods: Male Sprague-Dawley rats were infused with 20 mL of 4.25% glucose-based standard PD fluid for 8 consecutive weeks to establish PF model and then divided into five groups: Control, received sham operation and 0.9% physiological saline; PD, received 4.25% standard PD fluid; Curcumin, PD rats injected intraperitoeally with curcumin for 8 weeks at doses of 10, 20 or 40 mg/kg. Masson's staining was performed to evaluate the extent of PF. Peritoneal Equilibration Test (PET) was conducted to assess ultrafiltration volume (UFV) and mass transfer of glucose (MTG), quantitative RT-PCR, and immunohistochemistry or western blotting were performed to measure the expression levels of inflammation and fibrosis-associated factors. We also detected the TGF-β1 in peritoneal fluid by ELISA.<br />Results: Compared with the control group, the PD rats showed decreased UFV (2.54 ± 0.48 to 9.87 ± 0.78 mL, p < 0.05] and increased MTG (18.99 ± 0.86 to 10.85 ± 0.65 mmol/kg, p < 0.05) as well as obvious fibroproliferative response, with markedly increased peritoneal thickness (178.33 ± 4.42 to 25.26 ± 0.32um, p < 0.05) and higher expression of a-SMA, collagen I and TGF-β1. Treatment with curcumin significantly increased UFV, reduced MTG and peritoneal thickness of PD rats. The elevated TGF-β1 in peritoneal fluid of PD rats was significantly decreased by curcumin. It attenuated the increase in protein and mRNA of TGF-β1, α-SMA and collagen I in peritoneum of PD rats. The mRNA expressions of TAK1, JNK and p38, as well as the protein expressions of p-TAK1, p-JNK and p-p38 in peritoneum of PD rats were reduced by curcumin.<br />Conclusions: Present results demonstrate that curcumin showed a protective effect on PD-related PF and suggest an implication of TAK1, p38 and JNK pathway in mediating the benefical effects of curcumin.
- Subjects :
- Actins genetics
Actins metabolism
Animals
Collagen Type I genetics
Collagen Type I metabolism
Humans
MAP Kinase Kinase Kinases genetics
Male
Peritoneal Fibrosis etiology
Peritoneal Fibrosis genetics
Peritoneal Fibrosis metabolism
Peritoneum drug effects
Peritoneum metabolism
Rats
Rats, Sprague-Dawley
Signal Transduction
Transforming Growth Factor beta1 metabolism
Curcumin administration & dosage
MAP Kinase Kinase Kinases metabolism
Peritoneal Dialysis adverse effects
Peritoneal Fibrosis drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1472-6882
- Volume :
- 19
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC complementary and alternative medicine
- Publication Type :
- Academic Journal
- Accession number :
- 31647008
- Full Text :
- https://doi.org/10.1186/s12906-019-2702-6