An Overview of Carcinogenic Heavy Metal: Molecular Toxicity Mechanism and Prevention

Kim, Hyun Soo; Kim, Yeo Jin; Seo, Young Rok

doi:10.15430/jcp.2015.20.4.232

Cited by 498 publications

(278 citation statements)

References 91 publications

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“…Heavy metal poisoning has been a focus of public health research4121718. As one of the most easily accumulated poisonous substances in human body, lead exposure is closely related to chronic renal injury10111920.…”

Section: Discussionmentioning

confidence: 99%

Urinary KIM-1: a novel biomarker for evaluation of occupational exposure to lead

Zhou

Shen

et al. 2016

Sci Rep

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Chronic occult lead poisoning often develops ensuing occupational lead exposure. Early diagnosis of lead poisoning is critical for timely discontinuation of lead exposure and for prognosis. This study explored the value of urinary kidney injury molecule-1 (KIM-1) in diagnosing renal injury induced by lead at an early stage. We retrospectively analyzed 92 workers exposed to occupational lead and demonstrated a better correlation ship between blood lead levels and urine excretion of KIM-1 than other traditional renal injury biomarkers following creatinine adjustment. Receiver operating characteristic curve analysis of the ability of diverse biomarkers for predicting kidney injury in lead-exposed workers demonstrated that the order of predicting accuracy of the studied biomarkers is as follows: urinary KIM-1-to-creatinine ratio > urinary N-acetyl-β-(D)-glucosaminidase-to-creatinine ratio > urinary β2-microglobulin-to-creatinine ratio > urinary α1-microglobulin-to-creatinine ratio, with the Youden index being 16.59 ng/g, 14.01 U/g, 0.15 mg/g, and 4.63 mg/g, respectively. Collectively, our findings suggest that short-period occupational lead exposure may cause injury of renal tubules. Urinary excretion of KIM-1 correlates with blood lead levels better than other traditional renal injury biomarkers, including N-acetyl-β-(D)-glucosaminidase, α1-microglobulin, and β2-microglobulin. Longitudinal surveillance of urinary KIM-1 may aid for early diagnosis of renal tubular injury in workers with occupational lead exposure.

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Section: Discussionmentioning

confidence: 99%

Urinary KIM-1: a novel biomarker for evaluation of occupational exposure to lead

Zhou

Shen

et al. 2016

Sci Rep

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“…Exposure to arsenic has been associated with cancer, diabetes, cardiovascular disease, and metabolic syndrome (Singh et al 2011, Maull et al 2012, Kim et al 2015, Mohammed Abdul et al 2015). It has been suggested that arsenic alters common pathways such as those involved in oxidative stress and inflammatory signaling, which underlie a variety of arsenic-associated diseases (States et al 2009, Straif et al 2009, Mo et al 2011, Kim et al 2015).…”

Section: Introductionmentioning

confidence: 99%

“…It has been suggested that arsenic alters common pathways such as those involved in oxidative stress and inflammatory signaling, which underlie a variety of arsenic-associated diseases (States et al 2009, Straif et al 2009, Mo et al 2011, Kim et al 2015). The generation of ROS in particular is a major pathological mechanism induced by arsenic and is involved in the pathogenesis of cancer (Shi et al 2004), insulin resistance (Padmaja Divya et al 2015), metabolic syndrome (Ando et al 2009), and cardiovascular disease (States et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Monomethylarsonous acid, but not inorganic arsenic, is a mitochondria-specific toxicant in vascular smooth muscle cells

Pace

Banerjee

Welch

et al. 2016

Toxicology in Vitro

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Arsenic exposure has been implicated as a risk factor for cardiovascular diseases, metabolic disorders, and cancer, yet the role mitochondrial dysfunction plays in the cellular mechanisms of pathology is largely unknown. To investigate arsenic-induced mitochondrial dysfunction in vascular smooth muscle cells (VSMCs), we exposed rat aortic smooth muscle cells (A7r5) to inorganic arsenic (iAs(III)) and its metabolite monomethylarsonous acid (MMA(III)) and compared their effects on mitochondrial function and oxidative stress. Our results indicate that MMA(III) is significantly more toxic to mitochondria than iAs(III). Exposure of VSMCs to MMA(III), but not iAs(III), significantly decreased basal and maximal oxygen consumption rates and concomitantly increased compensatory extracellular acidification rates, a proxy of glycolysis. Treatment with MMA(III) significantly increased hydrogen peroxide and superoxide levels compared to iAs(III). Exposure to MMA(III) resulted in significant decreases in mitochondrial ATP, aberrant perinuclear clustering of mitochondria, and decreased mitochondrial content. Mechanistically, we observed that mitochondrial superoxide and hydrogen peroxide contribute to mitochondrial toxicity, as treatment of cells with MnTBAP (a mitochondrial superoxide dismutase mimetic) and catalase significantly reduced mitochondrial respiration deficits and cell death induced by both arsenic compounds. Overall, our data demonstrates that MMA(III) is a mitochondria-specific toxicant that elevates mitochondrial and non-mitochondrial sources of ROS.

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“…Although the adverse health effects of Cd are wellknown and the underlying mechanisms have been disclosed in degrees (see our review: Koedrith and Seo, 2011;Kwon et al, 2013;Kim et al, 2015), exposure to Cd is still being reported in some parts of the world (Ikeda et al, 2004;Pan et al, 2010;Waseem et al, 2014;Wang et al, 2015;Johnson et al, 2016). In addition to its discharge from mines, the emission of Cd has markedly increased since the late 20th century.…”

Section: Resultsmentioning

confidence: 98%

A pilot study for construction of a new cadmium-sensing yeast strain carrying a reporter plasmid with the <i>JLP1</i> promoter

et al. 2017

Self Cite

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-Cadmium contamination still occurs in some parts of the world, and its concentrations in the environment are monitored in most countries due to its adverse effects on human health. We herein established yeast (Saccharomyces cerevisiae) reporter assay strains carrying plasmids with the yeast JLP1, SEO1, and CUP1 promoters connected to the bacterial lacZ reporter gene. The strain carrying the high-copy number pESC-JLP1-lacZ reporter plasmid was more responsive to cadmium than strains with other reporter plasmids. This JLP1-lacZ reporter assay strain will be useful for monitoring cadmium contamination in environmental water and soil as a first screening tool preceding official instrumental analyses, because the assay is rapid, easy to handle, and has the ability to process a large number of samples at a low cost.

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An Overview of Carcinogenic Heavy Metal: Molecular Toxicity Mechanism and Prevention

Cited by 498 publications

References 91 publications

Urinary KIM-1: a novel biomarker for evaluation of occupational exposure to lead

Urinary KIM-1: a novel biomarker for evaluation of occupational exposure to lead

Monomethylarsonous acid, but not inorganic arsenic, is a mitochondria-specific toxicant in vascular smooth muscle cells

A pilot study for construction of a new cadmium-sensing yeast strain carrying a reporter plasmid with the <i>JLP1</i> promoter

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