Puerarin alleviated oxidative stress and ferroptosis during renal fibrosis induced by ischemia/reperfusion injury via TLR4/Nox4 pathway in rats

ABSTRACT Purpose: To investigate the role of puerarin on renal fibrosis and the underlying mechanism in renal ischemia and reperfusion (I/R) model. Methods: Rats were intraperitoneally injected with puerarin (50 or 100 mg/kg) per day for one week before renal I/R. The level of renal collagen depos...

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Main Authors: Jun Jian, Dan Wang, Yufeng Xiong, Jingsong Wang, Qingyuan Zheng, Zhengyu Jiang, Jiacheng Zhong, Song Yang, Lei Wang
Format: Article
Language:English
Published: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia 2023-08-01
Series:Acta Cirúrgica Brasileira
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-86502023000100219&tlng=en
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author Jun Jian
Dan Wang
Yufeng Xiong
Jingsong Wang
Qingyuan Zheng
Zhengyu Jiang
Jiacheng Zhong
Song Yang
Lei Wang
author_facet Jun Jian
Dan Wang
Yufeng Xiong
Jingsong Wang
Qingyuan Zheng
Zhengyu Jiang
Jiacheng Zhong
Song Yang
Lei Wang
author_sort Jun Jian
collection DOAJ
description ABSTRACT Purpose: To investigate the role of puerarin on renal fibrosis and the underlying mechanism in renal ischemia and reperfusion (I/R) model. Methods: Rats were intraperitoneally injected with puerarin (50 or 100 mg/kg) per day for one week before renal I/R. The level of renal collagen deposition and interstitial fibrosis were observed by hematoxylin and eosin and Sirius Red staining, and the expression of α-smooth muscle actin (α-SMA) was examined by immunohistochemical staining. The ferroptosis related factors and TLR4/Nox4-pathway-associated proteins were detected by Western blotting. Results: Puerarin was observed to alleviate renal collagen deposition, interstitial fibrosis and the α-SMA expression induced by I/R. Superoxide dismutase (SOD) activities and glutathione (GSH) level were decreased in I/R and hypoxia/reoxygenation (H/R), whereas malondialdehyde (MDA) and Fe2+ level increased. However, puerarin reversed SOD, MDA, GSH and Fe2+ level changes induced by I/R and H/R. Besides, Western blot indicated that puerarin inhibited the expression of ferroptosis related factors in a dose-dependent manner, which further demonstrated that puerarin had the effect to attenuate ferroptosis. Moreover, the increased expression of TLR/Nox4-pathway-associated proteins were observed in I/R and H/R group, but puerarin alleviated the elevated TLR/Nox4 expression. Conclusions: Our results suggested that puerarin inhibited oxidative stress and ferroptosis induced by I/R and, thus, delayed the progression of renal fibrosis, providing a new target for the treatment of renal fibrosis.
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spelling doaj.art-d72eac92cacd497da14aca2c7901f0512023-08-08T07:41:34ZengSociedade Brasileira para o Desenvolvimento da Pesquisa em CirurgiaActa Cirúrgica Brasileira1678-26742023-08-013810.1590/acb382523Puerarin alleviated oxidative stress and ferroptosis during renal fibrosis induced by ischemia/reperfusion injury via TLR4/Nox4 pathway in ratsJun Jianhttps://orcid.org/0000-0002-1406-4668Dan Wanghttps://orcid.org/0009-0006-8685-2635Yufeng Xionghttps://orcid.org/0000-0001-9810-1691Jingsong Wanghttps://orcid.org/0009-0005-7304-4607Qingyuan Zhenghttps://orcid.org/0000-0003-4682-3857Zhengyu Jianghttps://orcid.org/0009-0004-1783-6442Jiacheng Zhonghttps://orcid.org/0009-0008-7287-570XSong Yanghttps://orcid.org/0000-0002-8117-0970Lei Wanghttps://orcid.org/0000-0001-8412-1130ABSTRACT Purpose: To investigate the role of puerarin on renal fibrosis and the underlying mechanism in renal ischemia and reperfusion (I/R) model. Methods: Rats were intraperitoneally injected with puerarin (50 or 100 mg/kg) per day for one week before renal I/R. The level of renal collagen deposition and interstitial fibrosis were observed by hematoxylin and eosin and Sirius Red staining, and the expression of α-smooth muscle actin (α-SMA) was examined by immunohistochemical staining. The ferroptosis related factors and TLR4/Nox4-pathway-associated proteins were detected by Western blotting. Results: Puerarin was observed to alleviate renal collagen deposition, interstitial fibrosis and the α-SMA expression induced by I/R. Superoxide dismutase (SOD) activities and glutathione (GSH) level were decreased in I/R and hypoxia/reoxygenation (H/R), whereas malondialdehyde (MDA) and Fe2+ level increased. However, puerarin reversed SOD, MDA, GSH and Fe2+ level changes induced by I/R and H/R. Besides, Western blot indicated that puerarin inhibited the expression of ferroptosis related factors in a dose-dependent manner, which further demonstrated that puerarin had the effect to attenuate ferroptosis. Moreover, the increased expression of TLR/Nox4-pathway-associated proteins were observed in I/R and H/R group, but puerarin alleviated the elevated TLR/Nox4 expression. Conclusions: Our results suggested that puerarin inhibited oxidative stress and ferroptosis induced by I/R and, thus, delayed the progression of renal fibrosis, providing a new target for the treatment of renal fibrosis.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-86502023000100219&tlng=enChronic Kidney DiseaseFerroptosisReperfusion InjuryOxidative Stress
spellingShingle Jun Jian
Dan Wang
Yufeng Xiong
Jingsong Wang
Qingyuan Zheng
Zhengyu Jiang
Jiacheng Zhong
Song Yang
Lei Wang
Puerarin alleviated oxidative stress and ferroptosis during renal fibrosis induced by ischemia/reperfusion injury via TLR4/Nox4 pathway in rats
Acta Cirúrgica Brasileira
Chronic Kidney Disease
Ferroptosis
Reperfusion Injury
Oxidative Stress
title Puerarin alleviated oxidative stress and ferroptosis during renal fibrosis induced by ischemia/reperfusion injury via TLR4/Nox4 pathway in rats
title_full Puerarin alleviated oxidative stress and ferroptosis during renal fibrosis induced by ischemia/reperfusion injury via TLR4/Nox4 pathway in rats
title_fullStr Puerarin alleviated oxidative stress and ferroptosis during renal fibrosis induced by ischemia/reperfusion injury via TLR4/Nox4 pathway in rats
title_full_unstemmed Puerarin alleviated oxidative stress and ferroptosis during renal fibrosis induced by ischemia/reperfusion injury via TLR4/Nox4 pathway in rats
title_short Puerarin alleviated oxidative stress and ferroptosis during renal fibrosis induced by ischemia/reperfusion injury via TLR4/Nox4 pathway in rats
title_sort puerarin alleviated oxidative stress and ferroptosis during renal fibrosis induced by ischemia reperfusion injury via tlr4 nox4 pathway in rats
topic Chronic Kidney Disease
Ferroptosis
Reperfusion Injury
Oxidative Stress
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-86502023000100219&tlng=en
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