Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 99, Issue -, Pages 313-318Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2018.01.078
Keywords
Sepsis; Dihydroartemisinin; Glomerular endothelial cells; Permeability; Occludin
Funding
- Traditional Chinese Medicine Research Projects of Shandong Province [2015-285]
- Natural Science Foundation of Shandong Province [ZR2014HM043]
- Shandong Taishan Scholarship
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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 25 mu M, 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-alpha (TNF-alpha)-induced hyperpermeability of HRGEC monolayers. We found that TNF-alpha 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.
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