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Abstract: FR-PO1051

Piperazine Ferulate Regulates Renal Fibrosis by Alleviating Oxidative Stress in Renal Tubular Epithelial Cells

Session Information

Category: CKD (Non-Dialysis)

  • 2303 CKD (Non-Dialysis): Mechanisms

Authors

  • Yu, Min, Sichuan Provincial People’s Hospital, Yibin, Sichuan, China
  • Zhong, Xiang, Sichuan Provincial People’s Hospital, Yibin, Sichuan, China
  • Li, Yi, Sichuan Provincial People’s Hospital, Yibin, Sichuan, China
  • Liu, Kaixiang, Sichuan Provincial People’s Hospital, Yibin, Sichuan, China
  • Wang, Li, Sichuan Provincial People’s Hospital, Yibin, Sichuan, China
  • Li, Guisen, Sichuan Provincial People’s Hospital, Yibin, Sichuan, China
Background

Chronic kidney disease (CKD) is one of the greatest public health hazards worldwide with a high mortality rate, poor quality of survival. Oxidative stress in CKD could aggravate tubular injury to renal fibrosis. The treatment of oxidative damage to renal tubular epithelial cells still needs extensive research and development of drugs. This study was conducted to explore the effect of piperazine ferulate on renal fibrosis and the antioxidant mechanism of renal tubular epithelium and to provide a theoretical basis for the application of piperazine ferulate in CKD.

Methods

36 male C57 mice at 6-8 weeks were randomly divided into six groups (n=6): sham group (saline 0.2 mL), UUO group (saline 0.2 mL), piperazine ferulate low-dose intervention in UUO group (piperazine ferulate 50 mg/kg, 0.2 mL ), piperazine ferulate medium-dose in UUO group (piperazine ferulate 100mg/kg,0.2 mL ), piperazine ferulate high dose in UUO group (piperazine ferulate 200mg/kg,0.2 mL), and piperazine ferulate alone (piperazine ferulate 200mg/kg,0.2 mL ). The mice were then anesthetized and executed on the 7th day after surgery, and the relevant samples were collected and stained with HE, PAS and Masson to observe the tubular shape, atrophy, necrosis and the degree of interstitial fibrosis, and the fibrosis-related indexes FN, collagen-1, αSMA and p-Smd3 were observed by immunohistochemistry or protein blotting. The safe concentration range of piperazine ferulate in HK2 cells was screened by CCK8 in vitro and IC50 was calculated to select a safe concentration for intervention in TGF β-treated HK2 cells, subsequently protein blotting was used to detect FN, collagen-1, p-Smad3, KIM-1, HO-1 and dichlorofluorescein (DCF) was revealed in HK2 cells after intervention. of renal tubular epithelial cells were detected by protein blotting.

Results

Pathological staining showed that the fibrosis, renal tubular epithelial injury and oxidative stress significantly ameliorated in UUO mice after piperazine ferulate treatment at a dosage dependent manner, compared to that of sham-operated group. We also observed the same phenomenon in the HK2 cells with piperazine ferulate treatments upon TGF β stimulation.

Conclusion

Piperazine ferulate could significantly alleviate oxidative stress injury in renal tubular epithelial cells against renal fibrosis.

Funding

  • Government Support – Non-U.S.