Isoliquiritigenin attenuates septic acute kidney injury by regulating ferritinophagy-mediated ferroptosis

Defined differently from apoptosis, necrosis, and autophagy, ferroptosis has been implicated in acute kidney injury (AKI) such as ischemia-reperfusion injury induced AKI, folic acid caused AKI and cisplatin induced AKI. However, whether ferroptosis is involved in LPS induced AKI could be remaining u...

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Autores principales:	Yun Tang, Haojun Luo, Qiong Xiao, Li Li, Xiang Zhong, Jiong Zhang, Fang Wang, Guisen Li, Li Wang, Yi Li
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	acute kidney injury isoliquiritigenin ferroptosis ferritinophagy lipid peroxidation Diseases of the genitourinary system. Urology RC870-923
Acceso en línea:	https://doaj.org/article/c4e2a7bab648448d99fd00709d35939b
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spelling	oai:doaj.org-article:c4e2a7bab648448d99fd00709d35939b2021-11-26T11:19:46ZIsoliquiritigenin attenuates septic acute kidney injury by regulating ferritinophagy-mediated ferroptosis0886-022X1525-604910.1080/0886022X.2021.2003208https://doaj.org/article/c4e2a7bab648448d99fd00709d35939b2021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/0886022X.2021.2003208https://doaj.org/toc/0886-022Xhttps://doaj.org/toc/1525-6049Defined differently from apoptosis, necrosis, and autophagy, ferroptosis has been implicated in acute kidney injury (AKI) such as ischemia-reperfusion injury induced AKI, folic acid caused AKI and cisplatin induced AKI. However, whether ferroptosis is involved in LPS induced AKI could be remaining unclear and there is still a lack of therapies associated with ferroptosis in LPS induced AKI without side effects. This study aimed to elucidate the role of isoliquiritigenin (ISL) in ferroptosis of LPS-induced AKI. We used LPS to induce renal tubular injury, followed by treatment with ISL both in vitro and in vivo. Human renal tubular HK2 cells were pretreated with 50 μM or 100 μM ISL for 5 h before stimulation with 2 μg/mL LPS. Mice were administered a single dose of either 50 mg/kg ISL orally or 5 mg/kg ferroptosis inhibitor ferrostatin-1 intraperitoneally before 10 mg/kg LPS injection. We found that LPS could induce mitochondria injury of renal tubular presented as the shape of mitochondria appeared smaller than normal with increased membrane density and are faction or destruction of mitochondrial crista through scanning electron microscope. Ferrostatin-1 significantly protected mice against renal dysfunction and renal tubular damage in LPS-induced AKI. ISL inhibited Fe2+ and lipid peroxidation accumulation in LPS-stimulated HK2 cells. It also increased the expression of GPX4 and xCT, reduced the expression of HMGB1 and NCOA4 then attenuated mitochondria injury in renal tubular following LPS stimulation. These results indicated the potential role of ISL against ferritinophagy-mediated ferroptosis in renal tubular following LPS stimulation.Yun TangHaojun LuoQiong XiaoLi LiXiang ZhongJiong ZhangFang WangGuisen LiLi WangYi LiTaylor & Francis Grouparticleacute kidney injuryisoliquiritigeninferroptosisferritinophagylipid peroxidationDiseases of the genitourinary system. UrologyRC870-923ENRenal Failure, Vol 43, Iss 1, Pp 1551-1560 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	acute kidney injury isoliquiritigenin ferroptosis ferritinophagy lipid peroxidation Diseases of the genitourinary system. Urology RC870-923
spellingShingle	acute kidney injury isoliquiritigenin ferroptosis ferritinophagy lipid peroxidation Diseases of the genitourinary system. Urology RC870-923 Yun Tang Haojun Luo Qiong Xiao Li Li Xiang Zhong Jiong Zhang Fang Wang Guisen Li Li Wang Yi Li Isoliquiritigenin attenuates septic acute kidney injury by regulating ferritinophagy-mediated ferroptosis
description	Defined differently from apoptosis, necrosis, and autophagy, ferroptosis has been implicated in acute kidney injury (AKI) such as ischemia-reperfusion injury induced AKI, folic acid caused AKI and cisplatin induced AKI. However, whether ferroptosis is involved in LPS induced AKI could be remaining unclear and there is still a lack of therapies associated with ferroptosis in LPS induced AKI without side effects. This study aimed to elucidate the role of isoliquiritigenin (ISL) in ferroptosis of LPS-induced AKI. We used LPS to induce renal tubular injury, followed by treatment with ISL both in vitro and in vivo. Human renal tubular HK2 cells were pretreated with 50 μM or 100 μM ISL for 5 h before stimulation with 2 μg/mL LPS. Mice were administered a single dose of either 50 mg/kg ISL orally or 5 mg/kg ferroptosis inhibitor ferrostatin-1 intraperitoneally before 10 mg/kg LPS injection. We found that LPS could induce mitochondria injury of renal tubular presented as the shape of mitochondria appeared smaller than normal with increased membrane density and are faction or destruction of mitochondrial crista through scanning electron microscope. Ferrostatin-1 significantly protected mice against renal dysfunction and renal tubular damage in LPS-induced AKI. ISL inhibited Fe2+ and lipid peroxidation accumulation in LPS-stimulated HK2 cells. It also increased the expression of GPX4 and xCT, reduced the expression of HMGB1 and NCOA4 then attenuated mitochondria injury in renal tubular following LPS stimulation. These results indicated the potential role of ISL against ferritinophagy-mediated ferroptosis in renal tubular following LPS stimulation.
format	article
author	Yun Tang Haojun Luo Qiong Xiao Li Li Xiang Zhong Jiong Zhang Fang Wang Guisen Li Li Wang Yi Li
author_facet	Yun Tang Haojun Luo Qiong Xiao Li Li Xiang Zhong Jiong Zhang Fang Wang Guisen Li Li Wang Yi Li
author_sort	Yun Tang
title	Isoliquiritigenin attenuates septic acute kidney injury by regulating ferritinophagy-mediated ferroptosis
title_short	Isoliquiritigenin attenuates septic acute kidney injury by regulating ferritinophagy-mediated ferroptosis
title_full	Isoliquiritigenin attenuates septic acute kidney injury by regulating ferritinophagy-mediated ferroptosis
title_fullStr	Isoliquiritigenin attenuates septic acute kidney injury by regulating ferritinophagy-mediated ferroptosis
title_full_unstemmed	Isoliquiritigenin attenuates septic acute kidney injury by regulating ferritinophagy-mediated ferroptosis
title_sort	isoliquiritigenin attenuates septic acute kidney injury by regulating ferritinophagy-mediated ferroptosis
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/c4e2a7bab648448d99fd00709d35939b
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Isoliquiritigenin attenuates septic acute kidney injury by regulating ferritinophagy-mediated ferroptosis

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