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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Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia
2023-08-01
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Series: | Acta Cirúrgica Brasileira |
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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. |
first_indexed | 2024-03-12T16:56:09Z |
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issn | 1678-2674 |
language | English |
last_indexed | 2024-03-12T16:56:09Z |
publishDate | 2023-08-01 |
publisher | Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia |
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series | Acta Cirúrgica Brasileira |
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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