Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8526053 | Biomedicine & Pharmacotherapy | 2018 | 6 Pages |
Abstract
Sepsis, the systemic inflammatory responses after infection, remains a serious cause of morbidity and mortality in critically ill patients. The anti-malarial agent dihydroartemisinin (DHA) has been shown to be anti-inflammatory. In this study, we examined the effects of DHA on sepsis-induced acute kidney injury (AKI) and explored the mechanism underlying its mode of action in AKI. In a lipopolysaccharide (LPS)-induced mouse model, we observed that DHA treatment ameliorated glomerular injury, and relieved elevation of the urine albumin to creatinine ratio (UACR) and serum creatinine. At a concentration of 25â¯Î¼M, DHA had no effect on overall cellular viability or apoptosis in assays with human renal glomerular endothelial cells (HRGECs), but significantly inhibited the tumor necrosis factor-α (TNF-α)-induced hyperpermeability of HRGEC monolayers. We found that TNF-α decreases the expression of the junctional protein occludin in HRGECs, which is reversed by DHA. Taken together, our results demonstrate that DHA decreases permeability of the glomerular endothelium by maintenance of occludin expression. This suggests DHA may have therapeutic utility in sepsis-induced AKI.
Keywords
SBEUrine albumin creatinine ratioUACRGBMHUVECSGFBAKIdihydroartemisininLPSTGF-βVE-cadherinacute kidney injuryILSinterleukinsICUintensive care unittransforming growth factor-βtumor necrosis factor-αDHAHuman umbilical vein endothelial cellsglomerular endothelial cellsSepsisOccludinSmad-binding elementglomerular basement membraneTNF-αlipopolysaccharideglomerular filtration barrierPermeabilityvascular endothelial cadherin
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Authors
Zuowang Cheng, Ruixia Qi, Liqun Li, Qiang Liu, Wenqian Zhang, Xia Zhou, Dongmei Xu, Thaddeus D. Allen, Silin Pan, Ju Liu,