SP157INVESTIGATION OF THE PROTECTIVE EFFECTS OF ATORVASTATION ON CONTRAST-INDUCED ACUTE KIDNEY INJURY FROM THE PERSPECTIVE OF THE TLRA/MYD88 SIGNALING PATHWAY

Background and purpose: Increasing evidence suggests that ferroptosis plays a key role in the pathophysiology of acute kidney injury induced by cisplatin. The Nrf2 signaling pathway regulates oxidative stress and lipid peroxidation and positively regulates cisplatin-induced AKI (CI-AKI). However, Nrf2 and its activator leonurine on ferroptosis after CI-AKI remain unclear. Experimental Approach: The anti-ferroptotic effects of Nrf2 and its activator leonurine were assessed using a mouse model of cisplatin-induced AKI. In vitro, the potential effects of leonurine on erastin- and RSL3-induced HK-2 human PTEC ferroptosis were examined. Key Results: As expected, Nrf2 deletion induced ferroptosis-related protein expression and iron accumulation in vivo, further aggravating CI-AKI. The Nrf2 activator leonurine prevented iron accumulation and lipid peroxidation and inhibited ferroptosis in vitro, while these effects were abolished in siNrf2-treated cells. Moreover, leonurine potently ameliorated cisplatin-induced renal damage, as indicated by the assessment of SCr, BUN, KIM-1, and NGAL. Importantly, leonurine activated the Nrf2 antioxidative signaling pathway and prohibited changes in ferroptosis-related morphological and biochemical indicators, such as the MDA level, SOD and GSH depletion and GPX4 and xCT downregulation, in CI-AKI. Moreover, Nrf2 KO mice were more susceptible to ferroptosis after CI-AKI than control mice, and the protective effects of leonurine on AKI and ferroptosis were largely abolished in Nrf2 KO mice. Conclusion and Implications: These data suggest that the renal protective effects of Nrf2 and its activator leonurine on CI-AKI are achieved at least partially by inhibiting lipid peroxide-mediated ferroptosis and highlight the potential of leonurine as a CI-AKI treatment.

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Protective effects of dendropanoxide isolated from Dendropanax morbifera against cisplatin-induced acute kidney injury via the AMPK/mTOR signaling pathway

Food and Chemical Toxicology ◽

10.1016/j.fct.2020.111605 ◽

2020 ◽

Vol 145 ◽

pp. 111605

Author(s):

Yoo Jung Park ◽

Kyeong Seok Kim ◽

Jae Hyeon Park ◽

Song Hee Lee ◽

Hae Ri Kim ◽

...

Keyword(s):

Acute Kidney Injury ◽

Signaling Pathway ◽

Kidney Injury ◽

Mtor Signaling ◽

Protective Effects ◽

Mtor Signaling Pathway ◽

Dendropanax Morbifera

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Renal protective effects of alprostadil injection on early phase acute kidney injury after adult cardiopulmonary bypass

Academic Journal of Second Military Medical University ◽

10.3724/sp.j.1008.2010.00916 ◽

2010 ◽

Vol 30 (8) ◽

pp. 916-918

Author(s):

Qing XUE ◽

Bai-ling LI ◽

Zong WANG ◽

Tao YANG ◽

Keng ZHONG ◽

...

Keyword(s):

Acute Kidney Injury ◽

Cardiopulmonary Bypass ◽

Early Phase ◽

Kidney Injury ◽

Protective Effects

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Heme oxygenase-1 induction mitigates burn-associated early acute kidney injury via the TLR4 signaling pathway

Burns ◽

10.1016/j.burns.2021.04.013 ◽

2021 ◽

Author(s):

Songxue Guo ◽

Meirong Yu ◽

Quan Fang ◽

Liping Zhang ◽

Chuangang You ◽

...

Keyword(s):

Acute Kidney Injury ◽

Signaling Pathway ◽

Heme Oxygenase ◽

Kidney Injury ◽

Heme Oxygenase 1 ◽

Tlr4 Signaling ◽

Tlr4 Signaling Pathway

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Protective Effects of Carbon Dots Derived from Phellodendri Chinensis Cortex Carbonisata against Deinagkistrodon acutus Venom-Induced Acute Kidney Injury

Nanoscale Research Letters ◽

10.1186/s11671-019-3198-1 ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 2

Author(s):

Meiling Zhang ◽

Jinjun Cheng ◽

Ziwei Sun ◽

Hui Kong ◽

Yue Zhang ◽

...

Keyword(s):

Acute Kidney Injury ◽

Carbon Dots ◽

Biomedical Applications ◽

Abdominal Cavity ◽

Kidney Injury ◽

Protective Effects ◽

Inflammatory Reactions ◽

Chemotactic Protein ◽

Renal Histology ◽

Deinagkistrodon Acutus

Abstract Background As an emerging nanomaterial, carbon dots (CDs) have been the focus of tremendous attention for biomedical applications. However, little information is available on their bioactivity of inhibiting acute kidney injury (AKI) induced by snake venom. Methods This study reports the development of a green, one-step pyrolysis process to synthesize CDs using Phellodendri Chinensis Cortex (PCC) as the sole precursor, and their potential application as a protectant against Deinagkistrodon acutus (D. acutus) venom-induced AKI was investigated for the first time. The AKI model was established by injecting D. acutus venom into the abdominal cavity of mice and the potential protective effects of PCC Carbonisata-CDs (PCCC-CDs) on renal abnormalities including dysfunction, inflammatory reactions, tissue damage, and thrombocytopenia at six time points (1, 3, and 12 h, and 1, 2, and 5 days) were investigated. Results These results demonstrated that PCCC-CDs significantly inhibited the kidney dysfunction (reduced serum creatinine (SCR), blood urea nitrogen (BUN), urinary total protein (UTP), and microalbuminuria (MALB) concentrations) and the production of chemoattractant (monocyte chemotactic protein 1 (MCP-1)), proinflammatory cytokines (interleukin (IL)-1β), and anti-inflammatory cytokine (IL-10) in response to intraperitoneal injection of D. acutus venom. The beneficial effect of PCCC-CDs on the envenomed mice was similar to that on the change in renal histology and thrombocytopenia. Conclusions These results demonstrated the remarkable protective effects of PCCC-CDs against AKI induced by D. acutus venom, which would not only broaden the biomedical applications of CDs but also provide a potential target for the development of new therapeutic drugs for AKI induced by D. acutus snakebite envenomation.

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DNA demethylase Tet2 suppresses cisplatin-induced acute kidney injury

Cell Death Discovery ◽

10.1038/s41420-021-00528-7 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Yinwu Bao ◽

Mengqiu Bai ◽

Huanhuan Zhu ◽

Yuan Yuan ◽

Ying Wang ◽

...

Keyword(s):

Acute Kidney Injury ◽

Signaling Pathway ◽

Cell Injury ◽

Inflammatory Responses ◽

Kidney Injury ◽

Renal Tissue ◽

Clinical Samples ◽

Mice Model ◽

Expression Levels ◽

Ppar Signaling

AbstractDemethylase Tet2 plays a vital role in the immune response. Acute kidney injury (AKI) initiation and maintenance phases are marked by inflammatory responses and leukocyte recruitment in endothelial and tubular cell injury processes. However, the role of Tet2 in AKI is poorly defined. Our study determined the degree of renal tissue damage associated with Tet2 gene expression levels in a cisplatin-induced AKI mice model. Tet2-knockout (KO) mice with cisplatin treatment experienced severe tubular necrosis and dilatation, inflammation, and AKI markers’ expression levels than the wild-type mice. In addition, the administration of Tet2 plasmid protected Tet2-KO mice from cisplatin-induced nephrotoxicity, but not Tet2-catalytic-dead mutant. Tet2 KO was associated with a change in metabolic pathways like retinol, arachidonic acid, linolenic acid metabolism, and PPAR signaling pathway in the cisplatin-induced mice model. Tet2 expression is also downregulated in other AKI mice models and clinical samples. Thus, our results indicate that Tet2 has a renal protective effect during AKI by regulating metabolic and inflammatory responses through the PPAR signaling pathway.

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