Hemin mitigates contrast‐induced nephropathy by inhibiting ferroptosis via <scp>HO</scp>‐1/Nrf2/<scp>GPX4</scp> pathway

Gao, Zhao; Zhang, Ziyue; Gu, Daqian; Li, Yunqian; Zhang, Kun; Dong, Xiao; Liu, Lingli; Zhang, Jiye; Chen, Jimin; Wu, Duozhi; Zeng, Min

doi:10.1111/1440-1681.13673

Cited by 16 publications

(10 citation statements)

References 37 publications

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“…Ferroptosis is a form of programmed cell death that is dependent on iron and is characterized by abnormal mitochondrial structure, accumulation of lipid ROS and GSH. 33 , 34 Previous studies have shown that ferroptosis plays a detrimental role in the development of various forms of AKI, including CIN. To determine the protective effect of BBR against CIN, the inhibitory effect of BBR on ferroptosis was investigated.…”

Section: Resultsmentioning

confidence: 99%

“…The excessive accumulation of intracellular ROS, depletion of reductive GSH and release of intracellular Fe 2+ in large quantities from ferritin together induce ferroptosis 44 . It has been reported that CIN is closely associated with increased ferroptosis 34,45,46 . However, the microscopic morphology of cells undergoing ferroptosis during CIN has not been reported.…”

Section: Discussionmentioning

confidence: 99%

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Berberine alleviates contrast‐induced nephropathy by activating Akt/Foxo3a/Nrf2 signalling pathway

Wang,

Yu,

et al. 2023

J Cellular Molecular Medi

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Contrast‐induced nephropathy (CIN) is a condition that causes kidney damage in patients receiving angiography with iodine‐based contrast agents. This study investigated the potential protective effects of berberine (BBR) against CIN and its underlying mechanisms. The researchers conducted both in vivo and in vitro experiments to explore BBR's renal protective effects. In the in vivo experiments, SD rats were used to create a CIN model, and different groups were established. The results showed that CIN model group exhibited impaired renal function, severe damage to renal tubular cells and increased apoptosis and ferroptosis. However, BBR treatment group demonstrated improved renal function, decreased apoptosis and ferroptosis. Similar results were observed in the in vitro experiments using HK‐2 cells. BBR reduced ioversol‐induced apoptosis and ferroptosis, and exerted its protective effects through Akt/Foxo3a/Nrf2 signalling pathway. BBR administration increased the expression of Foxo3a and Nrf2 while decreasing the levels of p‐Akt and p‐Foxo3a. In conclusion, this study revealed that BBR effectively inhibited ioversol‐induced apoptosis and ferroptosis in vivo and in vitro. The protective effects of BBR were mediated through the modulation of Akt/Foxo3a/Nrf2 signalling pathway, leading to the alleviation of CIN. These findings suggest that BBR may have therapeutic potential for protecting against CIN in patients undergoing angiography with iodine‐based contrast agents.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Berberine alleviates contrast‐induced nephropathy by activating Akt/Foxo3a/Nrf2 signalling pathway

Wang,

Yu,

et al. 2023

J Cellular Molecular Medi

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“…Based on our results, we reason that using different models of injury (iron overload vs. IR) may explain the discrepant results. HO-1 has previously been reported to exert anti-ferroptotic properties [ 48 , 49 , 50 , 51 ]. Here, in corroboration of our previous findings in a model of kidney disease [ 18 ], we report that FtH deficiency leads to marked upregulation of HO-1 following injury.…”

Section: Discussionmentioning

confidence: 99%

Counteraction of Myocardial Ferritin Heavy Chain Deficiency by Heme Oxygenase-1

Machado

Spangler

Stacks

et al. 2022

IJMS

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Given the abundance of heme proteins (cytochromes) in the mitochondrion, it is evident that a meticulously orchestrated iron metabolism is essential for cardiac health. Here, we examined the functional significance of myocardial ferritin heavy chain (FtH) in a model of acute myocardial infarction. We report that FtH deletion did not alter either the mitochondrial regulatory and surveillance pathways (fission and fusion) or mitochondrial bioenergetics in response to injury. Furthermore, deletion of myocardial FtH did not affect cardiac function, assessed by measurement of left ventricular ejection fraction, on days 1, 7, and 21 post injury. To identify the modulated pathways providing cardiomyocyte protection coincident with FtH deletion, we performed unbiased transcriptomic analysis. We found that following injury, FtH deletion was associated with upregulation of several genes with anti-ferroptotic properties, including heme oxygenase-1 (HO-1) and the cystine/glutamate anti-porter (Slc7a11). These results suggested that HO-1 overexpression mitigates ferroptosis via upregulation of Slc7a11. Indeed, using transgenic mice with HO-1 overexpression, we demonstrate that overexpressed HO-1 is coupled with increased Slc7a11 expression. In conclusion, we demonstrate that following injury, myocardial FtH deletion leads to a compensatory upregulation in a number of anti-ferroptotic genes, including HO-1. Such HO-1 induction leads to overexpression of Slc7a11 and protects the heart against ischemia-reperfusion-mediated ferroptosis, preserves mitochondrial function, and overall function of the myocardium.

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“…Interestingly, in a contrast-induced nephropathy (CIN) model, type 1 diabetic rats received intravenous injection of iopromide, heme inhibited ferroptosis by activating HO-1/Nrf2 and upregulating GPX4. They suggested that HO-1 and Nrf2 constitute a positive mutually reinforcing cycle, resulting in self-reinforcement and maintenance of antioxidant capacity 137 . To date, the controversial points of HO-1 in ferroptosis might be dependent on the comprehensive regulation of iron content and antioxidant activity.…”

Section: Ferroptosis-related Regulators Involved In Dkdmentioning

confidence: 99%

Emerging Role of Ferroptosis in Diabetic Kidney Disease: Molecular Mechanisms and Therapeutic Opportunities

Wang¹,

Li²,

Zheng³

et al. 2023

Int. J. Biol. Sci.

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Diabetic kidney disease (DKD) is one of the most common and severe microvascular complications of diabetes mellitus (DM), and has become the leading cause of end-stage renal disease (ESRD) worldwide. Although the exact pathogenic mechanism of DKD is still unclear, programmed cell death has been demonstrated to participate in the occurrence and development of diabetic kidney injury, including ferroptosis. Ferroptosis, an iron-dependent form of cell death driven by lipid peroxidation, has been identified to play a vital role in the development and therapeutic responses of a variety of kidney diseases, such as acute kidney injury (AKI), renal cell carcinoma and DKD. In the past two years, ferroptosis has been well investigated in DKD patients and animal models, but the specific mechanisms and therapeutic effects have not been fully revealed. Herein, we reviewed the regulatory mechanisms of ferroptosis, summarized the recent findings associated with the involvement of ferroptosis in DKD, and discussed the potential of ferroptosis as a promising target for DKD treatment, thereby providing a valuable reference for basic study and clinical therapy of DKD.

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Hemin mitigates contrast‐induced nephropathy by inhibiting ferroptosis via HO‐1/Nrf2/GPX4 pathway

Cited by 16 publications

References 37 publications

Berberine alleviates contrast‐induced nephropathy by activating Akt/Foxo3a/Nrf2 signalling pathway

Berberine alleviates contrast‐induced nephropathy by activating Akt/Foxo3a/Nrf2 signalling pathway

Counteraction of Myocardial Ferritin Heavy Chain Deficiency by Heme Oxygenase-1

Emerging Role of Ferroptosis in Diabetic Kidney Disease: Molecular Mechanisms and Therapeutic Opportunities

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