Paeonol protects renal tubular cells against cadmium-induced cytotoxicity via alleviating oxidative stress, inhibiting inflammatory responses and restoring autophagy

被引:9
作者
Liu, Wenjing [1 ,2 ,3 ,4 ]
Gong, Zhonggui [1 ,2 ,3 ,4 ]
Zhang, Kanglei [1 ,2 ,3 ,4 ]
Dong, Wenxuan [1 ,2 ,3 ,4 ]
Zou, Hui [1 ,2 ,3 ,4 ]
Song, Ruilong [1 ,2 ,3 ,4 ]
Bian, Jianchun [1 ,2 ,3 ,4 ]
Zhu, Jiaqiao [1 ,2 ,3 ,4 ]
Liu, Gang [1 ,2 ,3 ,4 ]
Liu, Zongping [1 ,2 ,3 ,4 ]
机构
[1] Yangzhou Univ, Coll Vet Med, Yangzhou 225009, Jiangsu, Peoples R China
[2] Yangzhou Univ, Joint Int Res Lab Agr & Agriprod Safety, Minist Educ China, Yangzhou, Peoples R China
[3] Jiangsu Coinnovat Ctr Prevent & Control Important, Yangzhou 225009, Jiangsu, Peoples R China
[4] Jiangsu Key Lab Zoonosis, Yangzhou, Peoples R China
基金
中国国家自然科学基金;
关键词
Cadmium; Paeonol; Kidney; Oxidative stress; Inflammation; Autophagy; NF-KAPPA-B; INDUCED TOXICITY; EXPOSURE; KIDNEY; ROLES; NRF2; FLUX;
D O I
10.1016/j.jinorgbio.2022.111733
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cadmium (Cd) is a widespread environmental pollutant with highly toxic to kidney. Paeonol (Pae) is a natural flavonoid isolated from Moutan Cortex that exhibits antioxidant and anti-inflammatory properties. Herein, we investigated the protective effects of Pae against Cd-induced nephrotoxicity and elucidated its underlying mechanisms. First, we screened the optimum treatment conditions for Pae and confirmed its ability to protect NRK-52E cells against Cd-induced cytotoxicity. The results showed that Pae alleviated Cd-induced oxidative stress by scavenging excessive reactive oxygen species. Furthermore, Pae suppressed Cd-induced inflammatory responses by inhibiting the activation of nuclear factor-kappa B and the transcriptions of pro-inflammatory cytokines including cytokines including interleukin (IL)-1 beta, IL-6, monocyte chemotactic protein (MCP)-1 and tumour necrosis factor (TNF)-alpha. Pae alleviated Cd-induced autophagy inhibition, which was partly attributable to alleviation of oxidative stress. Meanwhile, Pae improved the structural integrity and degradation function of lysosomes, indicating that Pae can also target lysosomes to restore Cd-inhibited autophagic flux. Collectively, Pae alleviated Cd-induced renal cytotoxicity by alleviating oxidative stress, inhibiting inflammatory responses and restoring autophagy, implicating that Pae may serve as new candidate drug to treat Cd-induced nephrotoxicity.
引用
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页数:11
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