Research Paper Volume 12, Issue 22 pp 22744—22758
Geniposide ameliorated sepsis-induced acute kidney injury by activating PPARγ
- 1 Pharmacy Department, Tianjin Baodi Hospital, Baodi Clinical College of Tianjin Medical University, Tianjin 301800, China
- 2 Medicine Department, Peking University First Hospital, Beijing 100034, China
- 3 Pharmacy Department, Tianjin People's Hospital, Tianjin 300121, China
- 4 Pediatrics Department, First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin 150040, China
Received: April 21, 2020 Accepted: July 21, 2020 Published: November 10, 2020
https://doi.org/10.18632/aging.103902How to Cite
Copyright: © 2020 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Acute kidney injury is one of the most common complications that occurs in septic shock. An effective therapeutic intervention is urgently needed. Geniposide has been reported to possess pleiotropic activities against different diseases. However, the effect of geniposide on sepsis-induced kidney injury is unexplored. Our study aims to illustrate the mitigative effects of geniposide on sepsis-induced kidney injury and its relevant mechanisms. Sepsis was induced in mice undergoing cecal ligation and puncture (CLP) surgery. Mice were intraperitoneally injected with geniposide (10, 20 and 40 mg/kg) for treatment. The results showed that geniposide ameliorated kidney injury and dysfunction in CLP-induced septic mice, accompanied by reduction of inflammatory response and oxidative stress. We also found that geniposide significantly reduced vascular permeability and cellular apoptosis of the kidney, with increase of Bcl-2 and decrease of Bax and cleaved caspase-3. Moreover, PPARγ was found to be upregulated with the increasing concentration of geniposide. The protection of geniposide against inflammation and apoptosis was recovered by inhibition of PPARγ. Collectively, these results indicate that geniposide could significantly ameliorate acute kidney injury in CLP-induced septic mice and LPS-stimulated HK-2 cells by activating PPARγ. Geniposide might be a potential drug candidate for sepsis-induced kidney injury.
Abbreviations
GE: geniposide; CLP: cecal ligation and puncture; LPS: lipopolysaccharide; TNF-α: tumor necrosis factor-α; IL-6: interleukin-6; MCP-1: monocyte chemotactic protein 1; SOD: superoxide dismutase; MDA: malondialdehyde; GSH-px: glutathione peroxidase; ROS: reactive oxygen species; BUN: blood urea nitrogen; Scr: serum creatinine; ScysC: serum cystain C; α-GST: α glutathione S transferase; KIM1: kidney injury molecule 1; NGAL: neutrophil gelatinase-associated lipocalin; H&E: hematoxylin and eosin.