Environmental cadmium exposure and pancreatic cancer: Evidence from case control, animal and in vitro studies

Djordjević, Vladimir; Wallace, David R.; Schweitzer, Amie; Boričić, Novica; Knežević, Djordje; Matić, Slavko; Grubor, Nikola; Kerkez, Mirko; Radenković, Dejan; Bulat, Zorica; Antonijević, Biljana; Matović, Vesna; Buha, Aleksandra

doi:10.1016/j.envint.2019.04.048

Cited by 106 publications

(57 citation statements)

References 54 publications

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“…These mechanisms underlie the possible role of Cd as a metabolic disruptor. Its direct pancreatotoxic actions are buttressed by the Cd's ability to accumulate in the pancreas, as shown in many human studies [22,[38][39][40]. Similar results have been obtained in animal studies as well [41,42], with a dose-dependent accumulation pattern observed in rats [22].…”

Section: Introductionsupporting

confidence: 72%

Emerging Links between Cadmium Exposure and Insulin Resistance: Human, Animal, and Cell Study Data

Buha

Đukić-Ćosić

Ćurčić

et al. 2020

Toxics

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Recent research has helped clarify the role of cadmium (Cd) in various pathological states. We have demonstrated Cd involvement in pancreatic cancer, as well as the bioaccumulation of Cd in the pancreas. Bioaccumulation and increased toxicity suggest that Cd may also be involved in other pancreas-mediated diseases, like diabetes. Cd falls into the category of “hyperglycemic” metals, i.e., metals that increase blood glucose levels, which could be due to increased gluconeogenesis, damage to β-cells leading to reduced insulin production, or insulin resistance at target tissue resulting in a lack of glucose uptake. This review addresses the current evidence for the role of Cd, leading to insulin resistance from human, animal, and in vitro studies. Available data have shown that Cd may affect normal insulin function through multiple pathways. There is evidence that Cd exposure results in the perturbation of the enzymes and modulatory proteins involved in insulin signal transduction at the target tissue and mutations of the insulin receptor. Cd, through well-described mechanisms of oxidative stress, inflammation, and mitochondrial damage, may also alter insulin production in β-cells. More work is necessary to elucidate the mechanisms associated with Cd-mediated insulin resistance.

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Section: Introductionsupporting

confidence: 72%

Emerging Links between Cadmium Exposure and Insulin Resistance: Human, Animal, and Cell Study Data

Buha

Đukić-Ćosić

Ćurčić

et al. 2020

Toxics

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“…It was reported that cadmium intoxication intensified the generation of reactive oxygen species (ROS), depleted the endogenous antioxidant defenses, enhanced lipid peroxidation of cellular biomembranes and increased production of MDA, the end result of lipid peroxidation. [8][9][10] Additionally, upregulation of NF-κB-dependent inflammatory cascades with increased inflammatory cytokine production were involved in cadmium-induced tissue injury. 23 This is in consistence with the current investigation, which revealed that cadmium insult increased MDA, decreased GSH and CAT and raised NF-κB p65, TNF-α and IL-1β in the pancreatic tissue of rats.…”

Section: Discussionmentioning

confidence: 99%

“…8,9 It is also considered as a risk factor for pancreatic cancer in humans. 10 It was revealed that cadmium-induced oxidative stress up-regulated c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPKs) signaling pathways in pancreas, which resulted in enhancement of inflammatory responses and induction of apoptosis. 11…”

Section: Introductionmentioning

confidence: 99%

Naringenin and Vanillin Mitigate Cadmium-Induced Pancreatic Injury in Rats via Inhibition of JNK and p38 MAPK Pathways

Fouad¹,

Amin²,

Ahmed³

2020

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Chemicals NGN, VLN and CdCl 2 were purchased from Sigma-Aldrich, USA. VLN and CdCl 2 were ABSTRACT Background: Cadmium can induce pancreatic injury via oxidative stress, inflammation and apoptosis. Naringenin (NGN) and vanillin (VLN) exert antioxidant, anti-inflammatory, and antiapoptotic effects. Objective: The likely ameliorative effects of NGN, VLN and their combination were studied in rats exposed to cadmium-induced pancreatic injury. Materials and Methods: Rats received NGN (50 mg/kg/day, p.o.), VLN (100 mg/ kg/day, p.o.), or NGN + VLN for 7 days and one injection of CdCl 2 (2 mg/kg, i.p.) on the 6 th day. Results: Cadmium significantly lowered serum amylase and insulin levels. Cadmium also caused significant increments of malondialdehyde, tumor necrosis factor-α, interleukin-1β, nuclear factor-κB p65, Bax/Bcl-2 ratio and phosphorylated c-Jun N-terminal kinase (p-JNK) and p38 mitogen-activated protein kinases (MAPKs) and significant decrements of reduced glutathione and catalase in the pancreas of rats received CdCl 2. Additionally, CdCl 2 caused marked histopathological necrosis and significantly increased caspase-3 expression in pancreatic tissue. The cadmium-induced biochemical, histopathological and immunohistochemical changes were significantly ameliorated by NGN, VLN and NGN + VLN. However, NGN + VLN caused more significant ameliorative effects than did NGN and VLN alone. Conclusion: NGN, VLN and NGN + VLN afforded significant protection of pancreas in rats exposed to cadmium insult through modulation of JNK and p38 MAPK pathways and inhibition of oxidative stress, inflammation and apoptosis.

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“…Our understanding of the importance of miRNAs in cancer development has increased over the last few decades. The International Agency for Cancer Research (IARC) has classified Cd as a human carcinogen with a well-established association to kidney and prostatic cancers [62] as well as considerable involvement in other cancers, such as pancreatic cancer [63][64][65] and thyroid cancer [66], among which the role of miRNA in Cd-induced carcinogenesis is of great value. Evidence supporting the toxic metal modification of miRNA expression and cancer development is increasing, with Cd and As being two primary mediators [60,67].…”

Section: Cadmium-associated Changes In Mirna Expressionmentioning

confidence: 99%

Toxic-Metal-Induced Alteration in miRNA Expression Profile as a Proposed Mechanism for Disease Development

Wallace

Taalab

Heinze

et al. 2020

Cells

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Toxic metals are extensively found in the environment, households, and workplaces and contaminate food and drinking water. The crosstalk between environmental exposure to toxic metals and human diseases has been frequently described. The toxic mechanism of action was classically viewed as the ability to dysregulate the redox status, production of inflammatory mediators and alteration of mitochondrial function. Recently, growing evidence showed that heavy metals might exert their toxicity through microRNAs (miRNA)-short, single-stranded, noncoding molecules that function as positive/negative regulators of gene expression. Aberrant alteration of the endogenous miRNA has been directly implicated in various pathophysiological conditions and signaling pathways, consequently leading to different types of cancer and human diseases. Additionally, the gene-regulatory capacity of miRNAs is particularly valuable in the brain-a complex organ with neurons demonstrating a significant ability to adapt following environmental stimuli. Accordingly, dysregulated miRNAs identified in patients suffering from neurological diseases might serve as biomarkers for the earlier diagnosis and monitoring of disease progression. This review will greatly emphasize the effect of the toxic metals on human miRNA activities and how this contributes to progression of diseases such as cancer and neurodegenerative disorders (NDDs).

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Environmental cadmium exposure and pancreatic cancer: Evidence from case control, animal and in vitro studies

Cited by 106 publications

References 54 publications

Emerging Links between Cadmium Exposure and Insulin Resistance: Human, Animal, and Cell Study Data

Emerging Links between Cadmium Exposure and Insulin Resistance: Human, Animal, and Cell Study Data

Naringenin and Vanillin Mitigate Cadmium-Induced Pancreatic Injury in Rats via Inhibition of JNK and p38 MAPK Pathways

Toxic-Metal-Induced Alteration in miRNA Expression Profile as a Proposed Mechanism for Disease Development

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