Hispidulin Ameliorates Endotoxin-Induced Acute Kidney Injury in Mice

Lipopolysaccharide (LPS) is an endotoxin that plays a crucial role in septic acute kidney injury (AKI). Hispidulin is a natural flavonoid that possesses various biological activities. Recent studies have shown that hispidulin administration alleviates various inflammatory diseases in animal models....

Full description

Bibliographic Details
Main Authors: Kiryeong Kim, Jaechan Leem
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/6/2019
_version_ 1797444262063767552
author Kiryeong Kim
Jaechan Leem
author_facet Kiryeong Kim
Jaechan Leem
author_sort Kiryeong Kim
collection DOAJ
description Lipopolysaccharide (LPS) is an endotoxin that plays a crucial role in septic acute kidney injury (AKI). Hispidulin is a natural flavonoid that possesses various biological activities. Recent studies have shown that hispidulin administration alleviates various inflammatory diseases in animal models. This study aimed to investigate the renoprotective effect of hispidulin on LPS-induced AKI. Male C57BL/6 mice were administered LPS (10 mg/kg) with or without hispidulin (50 mg/kg). Hispidulin administration attenuated renal dysfunction, histological alterations, and the upregulation of neutrophil gelatinase-associated lipocalin. This flavonoid also reduced cytokine production and Toll-like receptor 4 expression, inhibited nuclear factor-κB and mitogen-activated protein kinase cascades, and alleviated immune cell infiltration. The oxidation of lipids and DNA was also inhibited by hispidulin administration. This antioxidant effect of hispidulin was associated with the downregulation of NADPH oxidase 4, the activation of catalase and superoxide dismutase activities, and the restoration of glutathione levels. Moreover, hispidulin administration attenuated tubular cell apoptosis by inhibiting caspase-3 pathway. These data suggest that hispidulin ameliorates endotoxin-induced kidney injury by suppressing inflammation, oxidative stress, and tubular cell death.
first_indexed 2024-03-09T13:09:04Z
format Article
id doaj.art-d56c998a318241bd87332183cb374c39
institution Directory Open Access Journal
issn 1420-3049
language English
last_indexed 2024-03-09T13:09:04Z
publishDate 2022-03-01
publisher MDPI AG
record_format Article
series Molecules
spelling doaj.art-d56c998a318241bd87332183cb374c392023-11-30T21:44:44ZengMDPI AGMolecules1420-30492022-03-01276201910.3390/molecules27062019Hispidulin Ameliorates Endotoxin-Induced Acute Kidney Injury in MiceKiryeong Kim0Jaechan Leem1Department of Immunology, School of Medicine, Daegu Catholic University, Daegu 42472, KoreaDepartment of Immunology, School of Medicine, Daegu Catholic University, Daegu 42472, KoreaLipopolysaccharide (LPS) is an endotoxin that plays a crucial role in septic acute kidney injury (AKI). Hispidulin is a natural flavonoid that possesses various biological activities. Recent studies have shown that hispidulin administration alleviates various inflammatory diseases in animal models. This study aimed to investigate the renoprotective effect of hispidulin on LPS-induced AKI. Male C57BL/6 mice were administered LPS (10 mg/kg) with or without hispidulin (50 mg/kg). Hispidulin administration attenuated renal dysfunction, histological alterations, and the upregulation of neutrophil gelatinase-associated lipocalin. This flavonoid also reduced cytokine production and Toll-like receptor 4 expression, inhibited nuclear factor-κB and mitogen-activated protein kinase cascades, and alleviated immune cell infiltration. The oxidation of lipids and DNA was also inhibited by hispidulin administration. This antioxidant effect of hispidulin was associated with the downregulation of NADPH oxidase 4, the activation of catalase and superoxide dismutase activities, and the restoration of glutathione levels. Moreover, hispidulin administration attenuated tubular cell apoptosis by inhibiting caspase-3 pathway. These data suggest that hispidulin ameliorates endotoxin-induced kidney injury by suppressing inflammation, oxidative stress, and tubular cell death.https://www.mdpi.com/1420-3049/27/6/2019endotoxinsepsisacute kidney injurynatural flavonoid
spellingShingle Kiryeong Kim
Jaechan Leem
Hispidulin Ameliorates Endotoxin-Induced Acute Kidney Injury in Mice
Molecules
endotoxin
sepsis
acute kidney injury
natural flavonoid
title Hispidulin Ameliorates Endotoxin-Induced Acute Kidney Injury in Mice
title_full Hispidulin Ameliorates Endotoxin-Induced Acute Kidney Injury in Mice
title_fullStr Hispidulin Ameliorates Endotoxin-Induced Acute Kidney Injury in Mice
title_full_unstemmed Hispidulin Ameliorates Endotoxin-Induced Acute Kidney Injury in Mice
title_short Hispidulin Ameliorates Endotoxin-Induced Acute Kidney Injury in Mice
title_sort hispidulin ameliorates endotoxin induced acute kidney injury in mice
topic endotoxin
sepsis
acute kidney injury
natural flavonoid
url https://www.mdpi.com/1420-3049/27/6/2019
work_keys_str_mv AT kiryeongkim hispidulinamelioratesendotoxininducedacutekidneyinjuryinmice
AT jaechanleem hispidulinamelioratesendotoxininducedacutekidneyinjuryinmice