• Ping-Hsun Yu, Yu-Hsuan Cheng, Shiu-Dong Chung, and Chiang-Ting Chien.
• Department of Life Science, School of Life Science, National Taiwan Normal University, Taipei, Taiwan, ROC.
• J Chin Med Assoc. 2024 Dec 1; 87 (12): 107810891078-1089.

BackgroundSepsis is a systemic inflammatory state associated with acute kidney injury (AKI) and high mortality. However, sepsis-induced AKI cannot be effectively prevented or treated using current antimicrobial therapies and supportive measures. We explored the therapeutic effect of newly developed fructose esters on sepsis-induced AKI (S-AKI).MethodsWe used the surface plasmon resonance technique and ultrasensitive chemiluminescence analyzer to characterize the lipopolysaccharide (LPS)/endotoxin binding activity and antioxidant capability of fructose esters. We assessed the extent of fructose ester gastrointestinal digestion using rat intestinal acetone powder. We examined the therapeutic effect of fructose esters on LPS-induced S-AKI by evaluating the blood and renal reactive oxygen species (ROS) amounts, caspase 1 mediated pyroptosis, inflammation, microcirculation, and renal dysfunction.ResultsOur data showed that the fructose esters are not easily hydrolyzed by the rat intestinal acetone powder, suggesting their high stability in the gastrointestinal tract. 1,6-dilauroyl-D-fructofuranose (FDL) dose-dependently scavenged H2O2 and displayed a higher binding affinity to LPS compared to sialic acid and fructose did. LPS significantly enhanced caspase 1 mediated pyroptosis and increased leukocyte infiltration, blood and renal ROS amount, and blood urea nitrogen (BUN) and creatinine level, whereas FDL significantly depressed these LPS-enhanced parameters. In addition, the increased plasma inflammatory cytokines levels using LPS could be reduced by intravenous fructose ester FDL treatment.ConclusionOur data suggest that FDL, with its antioxidant activity against H2O2, can neutralize LPS toxicity using a high binding affinity, and attenuate S-AKI by inhibiting caspase 1 mediated pyroptosis, thereby ameliorating renal oxidative stress and dysfunction.Copyright © 2024, the Chinese Medical Association.

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