Protective effect of platinum nano-antioxidant and nitric oxide against hepatic ischemia-reperfusion injury

Mu, Jing; Li, Chunxiao; Shi, Yu; Liu, Guoyong; Zou, Jianhua; Zhang, Dongyang; Jiang, Chao; Wang, Xiuli; He, Liangcan; Huang, Peng; Yin, Yuxin; Chen, Xiaoyuan

doi:10.1038/s41467-022-29772-w

Cited by 64 publications

(36 citation statements)

References 61 publications

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“…They show that a platinum nanoantioxidant can scavenge excessive reactive oxygen species at the injury site and meanwhile generate oxygen for subsequent synthesis of nitric oxide under the catalysis of nitric oxide synthase. Such cascade reaction successfully achieves dual protection for the liver through reactive oxygen species clearance and nitric oxide regulation, enabling reduction of oxidative stress, inhibition of macrophage activation and neutrophil recruitment and ensuring suppression of proinflammatory cytokines [ 53 ].…”

Section: Neutrophil-targeted Therapiesmentioning

confidence: 99%

Role of Immuno-Inflammatory Signals in Liver Ischemia-Reperfusion Injury

Kaltenmeier

Wang

Popp

et al. 2022

Cells

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Ischemia reperfusion injury (IRI) is a major obstacle in liver resection and liver transplantation. The initial step of IRI is mediated through ischemia which promotes the production of reactive oxygen species in Kupffer cells. This furthermore promotes the activation of pro-inflammatory signaling cascades, including tumor necrosis factor-alpha, IL-6, interferon, inducible nitric oxide synthase, TLR9/nuclear-factor kappa B pathway, and the production of damage-associated molecular patterns (DAMPs), such as ATP, histone, high mobility group box 1 (HMGB1), urate, mitochondrial formyl peptides and S100 proteins. With ongoing cell death of hepatocytes during the ischemic phase, DAMPs are built up and released into the circulation upon reperfusion. This promotes a cytokines/chemokine storm that attracts neutrophils and other immune cells to the site of tissue injury. The effect of IRI is further aggravated by the release of cytokines and chemokines, such as epithelial neutrophil activating protein (CXCL5), KC (CXCL1) and MIP-2 (CXCL2), the complement proteins C3a and C5a, mitochondrial-derived formyl peptides, leukotriene B4 and neutrophil extracellular traps (NETs) from migrating neutrophils. These NETs can also activate platelets and form Neutrophil-platelet microthrombi to further worsen ischemia in the liver. In this review we aim to summarize the current knowledge of mediators that promote liver IRI, and we will discuss the role of neutrophils and neutrophil extracellular traps in mediating IRI.

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Section: Neutrophil-targeted Therapiesmentioning

confidence: 99%

Role of Immuno-Inflammatory Signals in Liver Ischemia-Reperfusion Injury

Kaltenmeier

Wang

Popp

et al. 2022

Cells

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“…Blackberry leaf extract is a natural therapeutic medication with many regulatory actions, including improved microcirculation, suppression of apoptosis, and inhibition of neutrophil infiltration and inflammation [ 68 ]. For many years, blackberry-based therapy has been utilized for hepatic disorders and as a potent antioxidant [ 45 , 69 ]. Unfortunately, it is only effective at high doses which limited its clinical utility [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Blackberry-Loaded AgNPs Attenuate Hepatic Ischemia/Reperfusion Injury via PI3K/Akt/mTOR Pathway

et al. 2023

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Liver ischemia-reperfusion injury (IRI) is a pathophysiological insult that often occurs during liver surgery. Blackberry leaves are known for their anti-inflammatory and antioxidant activities. Aims: To achieve site-specific delivery of blackberry leaves extract (BBE) loaded AgNPs to the hepatocyte in IRI and to verify possible molecular mechanisms. Methods: IRI was induced in male Wister rats. Liver injury, hepatic histology, oxidative stress markers, hepatic expression of apoptosis-related proteins were evaluated. Non-targeted metabolomics for chemical characterization of blackberry leaves extract was performed. Key findings: Pre-treatment with BBE protected against the deterioration caused by I/R, depicted by a significant improvement of liver functions and structure, as well as reduction of oxidative stress with a concomitant increase in antioxidants. Additionally, BBE promoted phosphorylation of antiapoptotic proteins; PI3K, Akt and mTOR, while apoptotic proteins; Bax, Casp-9 and cleaved Casp-3 expressions were decreased. LC-HRMS-based metabolomics identified a range of metabolites, mainly flavonoids and anthocyanins. Upon comprehensive virtual screening and molecular dynamics simulation, the major annotated anthocyanins, cyanidin and pelargonidin glucosides, were suggested to act as PLA2 inhibitors. Significance: BBE can ameliorate hepatic IRI augmented by BBE-AgNPs nano-formulation via suppressing, oxidative stress and apoptosis as well as stimulation of PI3K/Akt/mTOR signaling pathway.

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“…However, clinical trials evaluating the efficacy of NAC yielded inconsistent results (reviewed in [ 124 ]). Whether ferroptosis inhibition will eventually make its way into the field of liver transplantation remains to be seen; presently, research efforts appear to be focused on machine perfusion strategies (reviewed in [ 125 ]) and on applying antioxidant nanoparticles with preferential liver uptake to reduce hepatic IRI [ 126 ], and we are not aware of any studies examining these substances in the context of ferroptosis.…”

Section: Therapeutic Relevance Of Ferroptosis Inhibitionmentioning

confidence: 99%

Progress and Setbacks in Translating a Decade of Ferroptosis Research into Clinical Practice

Samson-Himmelstjerna

Kolbrink

Riebeling

et al. 2022

Cells

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Ten years after its initial description, ferroptosis has emerged as the most intensely studied entity among the non-apoptotic forms of regulated cell death. The molecular features of ferroptotic cell death and its functional role have been characterized in vitro and in an ever-growing number of animal studies, demonstrating that it exerts either highly detrimental or, depending on the context, occasionally beneficial effects on the organism. Consequently, two contrary therapeutic approaches are being explored to exploit our detailed understanding of this cell death pathway: the inhibition of ferroptosis to limit organ damage in disorders such as drug-induced toxicity or ischemia-reperfusion injury, and the induction of ferroptosis in cancer cells to ameliorate anti-tumor strategies. However, the path from basic science to clinical utility is rocky. Emphasizing ferroptosis inhibition, we review the success and failures thus far in the translational process from basic research in the laboratory to the treatment of patients.

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Protective effect of platinum nano-antioxidant and nitric oxide against hepatic ischemia-reperfusion injury

Cited by 64 publications

References 61 publications

Role of Immuno-Inflammatory Signals in Liver Ischemia-Reperfusion Injury

Role of Immuno-Inflammatory Signals in Liver Ischemia-Reperfusion Injury

Blackberry-Loaded AgNPs Attenuate Hepatic Ischemia/Reperfusion Injury via PI3K/Akt/mTOR Pathway

Progress and Setbacks in Translating a Decade of Ferroptosis Research into Clinical Practice

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