Iron and iron-related proteins in alcohol consumers: cellular and clinical aspects

Ferrao, Kevin; Ali, Najma; Mehta, Kosha J.

doi:10.1007/s00109-022-02254-8

Cited by 12 publications

(7 citation statements)

References 89 publications

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“…But interestingly, non-drinkers and even nonsmokers in this study had higher sTfR levels instead. One previous study summarized that alcohol could alter the levels of some iron-related proteins, including serum iron, hepcidin and transferrin, which was not the case for sTfR (27). It indicated that there might be a more complex indirect interaction between alcohol consumption, sTfR and tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Associations between serum soluble transferrin receptor and the prevalence of cancers

et al. 2022

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BackgroundAs increasing experimental evidence suggests that iron metabolism play crucial roles in cancer and non-cancer conditions, there is a lack of data on serum soluble transferrin receptor (sTfR), a promising marker representing unmet cellular iron demands, between cancer risk from epidemiological studies. Here, we aimed to evaluate the predictive value of sTfR and cancer prevalence.Materials and methodsWe analyzed on 5,480 adult participants from 2015 to 2018 National Health and Nutrition Examination Survey (NHANES). Spearman correlation analysis was performed to investigate the correlations between sTfR and other characteristics. To identify the associations between sTfR and the prevalence of cancers, stratified multivariable logistic regression models, subgroup and sensitivity analyses were also performed.ResultsIn tertile analyses, participants in the highest level of sTfR were significantly associated with increased prevalence of total cancers [odds ratio (OR) = 1.53, 95% confidence interval (CI): 1.15-2.02] as compared with those at the lowest tertile. Each unit increment in ln-transformed sTfR concentration was shown to be associated with 39% increased risks of total cancers. Similar associations were found in males rather than females. Further subgroup and sensitivity analyses indicated that, in continuous and tertile analyses, sTfR was more closely associated with male- and female-specific cancers of prostate and testis (2.35: 1.03-5.40; 2.03: 1.00-4.09; respectively), and breast, cervix, ovary and uterus (1.92: 1.11-3.35; 1.66: 1.02-2.69; respectively).ConclusionsOur findings suggested that elevated level of sTfR was associated with the prevalence of cancers, especially in sex-specific cancers. In order to better determine them, further research in humans will be required.

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Section: Discussionmentioning

confidence: 99%

Associations between serum soluble transferrin receptor and the prevalence of cancers

et al. 2022

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“…Trace elements play an important role in human health and disease. For example, the role of iron in various diseases, including liver fibrosis, alcohol-related liver disease, and COVID-19, has been reviewed [157][158][159][160].…”

Section: Discussionmentioning

confidence: 99%

Role of zinc in health and disease

Stiles,

Ferrao,

Mehta

2024

Clin Exp Med

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This review provides a concise overview of the cellular and clinical aspects of the role of zinc, an essential micronutrient, in human physiology and discusses zinc-related pathological states. Zinc cannot be stored in significant amounts, so regular dietary intake is essential. ZIP4 and/or ZnT5B transport dietary zinc ions from the duodenum into the enterocyte, ZnT1 transports zinc ions from the enterocyte into the circulation, and ZnT5B (bidirectional zinc transporter) facilitates endogenous zinc secretion into the intestinal lumen. Putative promoters of zinc absorption that increase its bioavailability include amino acids released from protein digestion and citrate, whereas dietary phytates, casein and calcium can reduce zinc bioavailability. In circulation, 70% of zinc is bound to albumin, and the majority in the body is found in skeletal muscle and bone. Zinc excretion is via faeces (predominantly), urine, sweat, menstrual flow and semen. Excessive zinc intake can inhibit the absorption of copper and iron, leading to copper deficiency and anaemia, respectively. Zinc toxicity can adversely affect the lipid profile and immune system, and its treatment depends on the mode of zinc acquisition. Acquired zinc deficiency usually presents later in life alongside risk factors like malabsorption syndromes, but medications like diuretics and angiotensin-receptor blockers can also cause zinc deficiency. Inherited zinc deficiency condition acrodermatitis enteropathica, which occurs due to mutation in the SLC39A4 gene (encoding ZIP4), presents from birth. Treatment involves zinc supplementation via zinc gluconate, zinc sulphate or zinc chloride. Notably, oral zinc supplementation may decrease the absorption of drugs like ciprofloxacin, doxycycline and risedronate.

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“…Clinical studies have revealed that there are change in iron metabolism in substance use disorders including alcohol abuser. 28 – 31 , 52 , 53 A study conducted in chronic cocaine user revealed that iron content was significantly higher in basal ganglia reward regions than that of control individuals. 54 It was also reported that iron mediates morphine -induced ferritin heavy chain upregulation.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-inducible factor upregulation by roxadustat attenuates drug reward by altering brain iron homoeostasis

Yan,

Li,

et al. 2023

Sig Transduct Target Ther

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Substance use disorder remains a major challenge, with an enduring need to identify and evaluate new, translational targets for effective treatment. Here, we report the upregulation of Hypoxia-inducible factor-1α (HIF-1α) expression by roxadustat (Rox), a drug developed for renal anemia that inhibits HIF prolyl hydroxylase to prevent degradation of HIF-1α, administered either systemically or locally into selected brain regions, suppressed morphine (Mor)-induced conditioned place preference (CPP). A similar effect was observed with methamphetamine (METH). Moreover, Rox also inhibited the expression of both established and reinstated Mor-CPP and promoted the extinction of Mor-CPP. Additionally, the elevation of HIF-1α enhanced hepcidin/ferroportin 1 (FPN1)-mediated iron efflux and resulted in cellular iron deficiency, which led to the functional accumulation of the dopamine transporter (DAT) in plasma membranes due to iron deficiency-impaired ubiquitin degradation. Notably, iron-deficient mice generated via a low iron diet mimicked the effect of Rox on the prevention of Mor- or METH-CPP formation, without affecting other types of memory. These data reveal a novel mechanism for HIF-1α and iron involvement in substance use disorder, which may represent a potential novel therapeutic strategy for the treatment of drug abuse. The findings also repurpose Rox by suggesting a potential new indication for the treatment of substance use disorder.

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Iron and iron-related proteins in alcohol consumers: cellular and clinical aspects

Cited by 12 publications

References 89 publications

Associations between serum soluble transferrin receptor and the prevalence of cancers

Associations between serum soluble transferrin receptor and the prevalence of cancers

Role of zinc in health and disease

Hypoxia-inducible factor upregulation by roxadustat attenuates drug reward by altering brain iron homoeostasis

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