Disruption of essential metal homeostasis in the brain by cadmium and high-fat diet

Mazzocco, John C.; Jagadapillai, Rekha; Gozal, Evelyne; Kong, Maiying; Xu, Qiwu; Barnes, Gregory; Freedman, Jonathan H.

doi:10.1016/j.toxrep.2020.08.005

Cited by 16 publications

(7 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on the investigation of Mazzocco et al ( 2020 ), mice fed with a high-fat diet compared to a low-fat diet group showed significant increases in Cd levels.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Monitoring of metal content in the tissues of wild boar (Sus scrofa) and its food safety aspect

Lénárt

Bartha

Abonyi‐Tóth

et al. 2022

Environ Sci Pollut Res

View full text Add to dashboard Cite

The study was performed on 10 female and 10 male wild boars (Sus scrofa) after shooting during the regular hunting season to investigate the concentration of metals in the muscle and fat tissue. The concentrations of essential and non-essential elements were determined (arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb), manganese (Mn), mercury (Hg), and zinc (Zn)) using inductively coupled plasma optical emission spectrometry. The concentrations of As, Hg, and Cd were below the limit of detection (As, Hg: < 0.5 mg/kg, Cd: < 0.05 mg/kg) in every tissue sample of both sexes. The lead was detected as 0.36 ± 0.16 mg/kg and 0.22 ± 0.06 mg/kg in the muscle of females and males, respectively, showing a significant difference between the sexes (p = 0.0184). The measured concentration of Cr was 0.14 ± 0.08 mg/kg and 0.13 ± 0.06 mg/kg, and that of copper was 1.22 ± 0.14 mg/kg and 1.06 ± 0.16 mg/kg in the muscle of females and males, respectively. The same tendency was observed in the case of copper content of fat tissues (female: 0.13 ± 0.10 mg/kg; male: 0.13 ± 0.04 mg/kg; p = 0.2707). Manganese concentration of muscle was 0.45 ± 0.30 mg/kg (female) and 1.36 ± 0.96 mg/kg (male), and that of fat tissue was 0.32 ± 0.22 mg/kg (female) and 0.74 ± 0.75 mg/kg (male). The Zn was detected as 56.75 ± 7.86 mg/kg and 1.83 ± 0.76 mg/kg in the muscle and fat of females and 52.12 ± 11.51 mg/kg and 1.94 ± 0.57 mg/kg in males, respectively. Based on data, the consumption of fat and muscle tissues of the wild boars tested can be food toxicologically objectionable, mainly due to the lead content, and thus pose a risk to frequent consumers of this type of game meat.

show abstract

“…Based on the investigation of Mazzocco et al ( 2020 ), mice fed with a high-fat diet compared to a low-fat diet group showed significant increases in Cd levels.…”

Section: Resultsmentioning

confidence: 99%

“…High-fat diet significantly affected the levels of some essential metals, including chromium, copper, and zinc, in mice brains (Mazzocco et al 2020 ).…”

Section: Resultsmentioning

confidence: 99%

Monitoring of metal content in the tissues of wild boar (Sus scrofa) and its food safety aspect

Lénárt

Bartha

Abonyi‐Tóth

et al. 2022

Environ Sci Pollut Res

View full text Add to dashboard Cite

show abstract

“…Cadmium and obesity interact to exacerbate human pathologies including prediabetes, metabolic syndrome and hypertension [ [24] , [25] , [26] ]. Additionally, in identical animals, HFD increases the levels of cadmium in the heart, liver, kidney and brain [ 8 , 9 ]. Therefore, the impact of HFD on cadmium levels in the testis was also examined.…”

Section: Discussionmentioning

confidence: 99%

“…Although the major sites for cadmium accumulation and storage in mammals are the kidney followed by the liver, recent studies show cadmium also accumulates in the heart and brain [ 8 , 9 ]. Analysis of human autopsy tissue report significant levels of cadmium in testis, epididymis, prostate and seminal vesicles, which increases as a function of age [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of cadmium and high-fat diet on essential metal concentration in the mouse testis

Zhou

Gentry

et al. 2021

Toxicology Reports

Self Cite

View full text Add to dashboard Cite

show abstract

“…Cd is a ubiquitous heavy metal found in sewage, phosphate fertilizers, nickel–cadmium (NiCd) batteries, plated metal, plastics, and pigments [ 51 ]. It is enriched in the tobacco plant [ 52 ], and, upon overexposure, Cd can accumulate within the blood, kidneys, liver, reproductive organs, and motor control centers of the brain, specifically the parietal cortex, striatum, and cerebellum [ 53 , 54 , 55 ]. The long biological half-life of Cd (15–20 years) allows Cd to accumulate and induce metal dyshomeostasis, oxidative stress, mitochondrial dysfunction, and perturb protein degradation pathways, resulting in neurodegeneration [ 55 , 56 ].…”

Section: Introductionmentioning

confidence: 99%

Defective Mitochondrial Dynamics and Protein Degradation Pathways Underlie Cadmium-Induced Neurotoxicity and Cell Death in Huntington’s Disease Striatal Cells

Kamitsuka

Ghanem

Ziar

et al. 2023

IJMS

View full text Add to dashboard Cite

Exposure to heavy metals, including cadmium (Cd), can induce neurotoxicity and cell death. Cd is abundant in the environment and accumulates in the striatum, the primary brain region selectively affected by Huntington’s disease (HD). We have previously reported that mutant huntingtin protein (mHTT) combined with chronic Cd exposure induces oxidative stress and promotes metal dyshomeostasis, resulting in cell death in a striatal cell model of HD. To understand the effect of acute Cd exposure on mitochondrial health and protein degradation pathways, we hypothesized that expression of mHTT coupled with acute Cd exposure would cooperatively alter mitochondrial bioenergetics and protein degradation mechanisms in striatal STHdh cells to reveal novel pathways that augment Cd cytotoxicity and HD pathogenicity. We report that mHTT cells are significantly more susceptible to acute Cd-induced cell death as early as 6 h after 40 µM CdCl2 exposure compared with wild-type (WT). Confocal microscopy, biochemical assays, and immunoblotting analysis revealed that mHTT and acute Cd exposure synergistically impair mitochondrial bioenergetics by reducing mitochondrial potential and cellular ATP levels and down-regulating the essential pro-fusion proteins MFN1 and MFN2. These pathogenic effects triggered cell death. Furthermore, Cd exposure increases the expression of autophagic markers, such as p62, LC3, and ATG5, and reduces the activity of the ubiquitin–proteasome system to promote neurodegeneration in HD striatal cells. Overall, these results reveal a novel mechanism to further establish Cd as a pathogenic neuromodulator in striatal HD cells via Cd-triggered neurotoxicity and cell death mediated by an impairment in mitochondrial bioenergetics and autophagy with subsequent alteration in protein degradation pathways.

show abstract

Disruption of essential metal homeostasis in the brain by cadmium and high-fat diet

Abstract: Graphical abstract

Cited by 16 publications

References 58 publications

Monitoring of metal content in the tissues of wild boar (Sus scrofa) and its food safety aspect

Monitoring of metal content in the tissues of wild boar (Sus scrofa) and its food safety aspect

Effects of cadmium and high-fat diet on essential metal concentration in the mouse testis

Defective Mitochondrial Dynamics and Protein Degradation Pathways Underlie Cadmium-Induced Neurotoxicity and Cell Death in Huntington’s Disease Striatal Cells

Contact Info

Product

Resources

About