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.
Highlights
Sepsis, caused by dysregulated host response to infection, is deemed as a whole-body inflammatory response, which contributes to extensive tissue damage and multiple organ disorders
The result showed that the structure of glomerulus was clear and complete, and the kidney tubules were tightly packed in control and sham group
periodic acid-schiff (PAS) staining showed a severe histological kidney injury as glomerular basement membranes markedly thickened companied with glomerular hypertrophy in cecal ligation and puncture (CLP) group, which was attenuated by GE treatment (Figure 1B)
Summary
Sepsis, caused by dysregulated host response to infection, is deemed as a whole-body inflammatory response, which contributes to extensive tissue damage and multiple organ disorders. It has been the leading cause of death in intensive care units (ICUs) [1]. Despite the development of clinical care and intensive care, a specific and effective therapy for AKI is still inadequate. The incidence rate of AKI is up to 70%, and about 5% of the patients develop acute renal failure. The morality of AKI is about 50%, and 15% of survivors still depend on renal replacement therapy (RRT) after discharge, seriously threatening the life of people and troubling family and society [2, 3]. Excavation of new effective strategies for sepsisinduced AKI is important and urgently required
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