Affiliation:
1. Department of Immunology, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea
Abstract
Sepsis is a severe inflammatory condition that can cause organ dysfunction, including acute kidney injury (AKI). Hesperetin is a flavonoid aglycone that has potent antioxidant and anti-inflammatory properties. However, the effect of hesperetin on septic AKI has not yet been fully investigated. This study examined whether hesperetin has a renoprotective effect on lipopolysaccharide (LPS)-induced septic AKI. Hesperetin treatment ameliorated histological abnormalities and renal dysfunction in LPS-injected mice. Mechanistically, hesperetin attenuated LPS-induced oxidative stress, as evidenced by the suppression of lipid and DNA oxidation. This beneficial effect of hesperetin was accompanied by downregulation of the pro-oxidant NADPH oxidase 4, restoration of glutathione levels, and activation of antioxidant enzymes. This flavonoid compound also inhibited apoptotic cell death via suppression of p53-dependent caspase-3 pathway. Furthermore, hesperetin alleviated Toll-like receptor 4-mediated cytokine production and macrophage infiltration. Our findings suggest that hesperetin ameliorates LPS-induced renal structural and functional injury through suppressing oxidative stress, apoptosis, and inflammation.
Funder
Daegu Catholic University
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
Reference60 articles.
1. Characterization of Pathogenic Sepsis Etiologies and Patient Profiles: A Novel Approach to Triage and Treatment;Dolin;Microbiol. Insights,2019
2. Increasing Sepsis Rates in the United States: Results From National Inpatient Sample, 2005 to 2014;Rubens;J. Intensive Care Med.,2020
3. Sepsis-induced AKI: From pathogenesis to therapeutic approaches;He;Front. Pharmacol.,2022
4. Acute kidney injury and chronic kidney disease: An integrated clinical syndrome;Chawla;Kidney Int.,2012
5. Liu, J., Xie, H., Ye, Z., Li, F., and Wang, L. (2020). Rates, predictors, and mortality of sepsis-associated acute kidney injury: A systematic review and meta-analysis. BMC Nephrol., 21.
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