Gold- induced aplastic anemia

Williame, L. M. E.; Joos, Rik; Proot, F.; Immesoete, C.

doi:10.1007/bf02330601

Cited by 8 publications

(2 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specifically, in several case, patients treated with AUR developed anemia, and reducing or splitting the dose can alleviate these symptoms. 37 – 39 These clinical observation indicated AUR’s potent roles in iron metabolism, but still lack further mechanistic study. We therefore focused on examining the effects of AUR.…”

Section: Resultsmentioning

confidence: 99%

Auranofin mitigates systemic iron overload and induces ferroptosis via distinct mechanisms

Yang

Wang

Xiang

et al. 2020

Sig Transduct Target Ther

176

145

View full text Add to dashboard Cite

Iron homeostasis is essential for health; moreover, hepcidin-deficiency results in iron overload in both hereditary hemochromatosis and iron-loading anemia. Here, we identified iron modulators by functionally screening hepcidin agonists using a library of 640 FDA-approved drugs in human hepatic Huh7 cells. We validated the results in C57BL/6J mice and a mouse model of hemochromatosis (Hfe −/− mice). Our screen revealed that the anti-rheumatoid arthritis drug auranofin (AUR) potently upregulates hepcidin expression. Interestingly, we found that canonical signaling pathways that regulate iron, including the Bmp/Smad and IL-6/Jak2/Stat3 pathways, play indispensable roles in mediating AUR's effects. In addition, AUR induces IL-6 via the NF-κB pathway. In C57BL/6J mice, acute treatment with 5 mg/kg AUR activated hepatic IL-6/hepcidin signaling and decreased serum iron and transferrin saturation. Whereas chronically treating male Hfe −/− mice with 5 mg/kg AUR activated hepatic IL-6/hepcidin signaling, decreasing systemic iron overload, but less effective in females. Further analyses revealed that estrogen reduced the ability of AUR to induce IL-6/hepcidin signaling in Huh7 cells, providing a mechanistic explanation for ineffectiveness of AUR in female Hfe −/− mice. Notably, high-dose AUR (25 mg/kg) induces ferroptosis and causes lipid peroxidation through inhibition of thioredoxin reductase (TXNRD) activity. We demonstrate the ferroptosis inhibitor ferrostatin significantly protects liver toxicity induced by highdose AUR without comprising its beneficial effect on iron metabolism. In conclusion, our findings provide compelling evidence that TXNRD is a key regulator of ferroptosis, and AUR is a novel activator of hepcidin and ferroptosis via distinct mechanisms, suggesting a promising approach for treating hemochromatosis and hepcidin-deficiency related disorders.

show abstract

Section: Resultsmentioning

confidence: 99%

Auranofin mitigates systemic iron overload and induces ferroptosis via distinct mechanisms

Yang

Wang

Xiang

et al. 2020

Sig Transduct Target Ther

176

145

View full text Add to dashboard Cite

show abstract

“…Concerning adverse effects of Au compounds, a heterogeneous picture arises with regard to the immune system. On the one hand, several adverse effects can be connected to immunosuppression like impairment of macrophages, T and B cells, Ig deficiency, aplastic anemia, 719 as well as bone marrow suppression. 720 On the other hand, also immunestimulating reactions can occur.…”

Section: Gold (Au)mentioning

confidence: 99%

Metal Drugs and the Anticancer Immune Response

et al. 2018

View full text Add to dashboard Cite

The immune system deploys a multitude of innate and adaptive mechanisms not only to ward off pathogens but also to prevent malignant transformation ("immune surveillance"). Hence, a clinically apparent tumor already reflects selection for those malignant cell clones capable of evading immune recognition ("immune evasion"). Metal drugs, besides their well-investigated cytotoxic anticancer effects, massively interact with the cancer-immune interface and can reverse important aspects of immune evasion. This topic has recently gained intense attention based on combination approaches with anticancer immunotherapy (e.g., immune checkpoint inhibitors), a strategy recently delivering first exciting results in clinical settings. This review summarizes the promising but still extremely fragmentary knowledge on the interplay of metal drugs with the fidelity of anticancer immune responses but also their role in adverse effects. It highlights that, at least in some cases, metal drugs can induce long-lasting anticancer immune responses. Important steps in this process comprise altered visibility and susceptibility of cancer cells toward innate and adaptive immunity, as well as direct impacts on immune cell populations and the tumor microenvironment. On the basis of the gathered information, we suggest initiating joint multidisciplinary programs to implement comprehensive immune analyses into strategies to develop novel and smart anticancer metal compounds.

show abstract

Hematological Adverse Drug Reactions

Carey

2014

Mann's Pharmacovigilance

View full text Add to dashboard Cite

Gold- induced aplastic anemia

Cited by 8 publications

References 24 publications

Auranofin mitigates systemic iron overload and induces ferroptosis via distinct mechanisms

Auranofin mitigates systemic iron overload and induces ferroptosis via distinct mechanisms

Metal Drugs and the Anticancer Immune Response

Hematological Adverse Drug Reactions

Contact Info

Product

Resources

About