Cadmium induces oxidative stress and apoptosis in lung epithelial cells

Kumar, K. Ravi; Kumar, M. Naveen; Patil, Rajeshwari H.; Nagesh, Rashmi; Hegde, Shubha M.; Kavya, K. V.; Babu, R. L.; Ramesh, Govindarajan T.; Sharma, Shivangi

doi:10.1080/15376516.2016.1223240

Cited by 44 publications

(16 citation statements)

References 49 publications

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“…The mechanisms of Cd toxicity in lung cells may also involve endoplasmic reticulum (ER) stress ( Kim et al, 2017 ) and up-regulation of apoptosis ( Heo et al, 2017 ). Particularly, Cd exposure resulted in activation of proapoptotic signals (Bax, caspase 8) and repression of antiapoptotic Bcl-2 signaling in A549 lung cells ( Kiran Kumar et al, 2016 ). Apoptosis is also known to be involved in the regulation of Cd-induced autophagy in A549 cells (Li et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Toxic metal exposure as a possible risk factor for COVID-19 and other respiratory infectious diseases

Skalny

Lima

Tao

et al. 2020

Food and Chemical Toxicology

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Multiple medical, lifestyle, and environmental conditions, including smoking and particulate pollution, have been considered as risk factors for CO rona VI rus D isease 2019 (COVID-19) susceptibility and severity. Taking into account the high level of toxic metals in both particulate matter (PM2.5) and tobacco smoke, the objective of this review is to discuss recent data on the role of heavy metal exposure in development of respiratory dysfunction, immunotoxicity, and severity of viral diseases in epidemiological and experimental studies, as to demonstrate the potential crossroads between heavy metal exposure and COVID-19 severity risk. The existing data demonstrate that As, Cd, Hg, and Pb exposure is associated with respiratory dysfunction and respiratory diseases (COPD, bronchitis). These observations corroborate laboratory findings on the role of heavy metal exposure in impaired mucociliary clearance, reduced barrier function, airway inflammation, oxidative stress, and apoptosis. The association between heavy metal exposure and severity of viral diseases, including influenza and respiratory syncytial virus has been also demonstrated. The latter may be considered a consequence of adverse effects of metal exposure on adaptive immunity. Therefore, reduction of toxic metal exposure may be considered as a potential tool for reducing susceptibility and severity of viral diseases affecting the respiratory system, including COVID-19.

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Section: Introductionmentioning

confidence: 99%

Toxic metal exposure as a possible risk factor for COVID-19 and other respiratory infectious diseases

Skalny

Lima

Tao

et al. 2020

Food and Chemical Toxicology

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“…Cd is a toxic heavy metal. In vitro and in vivo studies have proven the toxic effects of Cd on a variety of tissues, including the liver [ 47 ], kidney [ 48 ], heart [ 49 ], lung [ 50 ], etc. Upon uptake into the body, Cd can complex with MT, a known heavy metal chelator, for detoxification [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Zinc protects against cadmium-induced toxicity in neonatal murine engineered cardiac tissues via metallothionein-dependent and independent mechanisms

Zhen

et al. 2019

Acta Pharmacol Sin

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Cadmium (Cd) is a nonessential heavy metal and a prevalent environmental toxin that has been shown to induce significant cardiomyocyte apoptosis in neonatal murine engineered cardiac tissues (ECTs). In contrast, zinc (Zn) is a potent metallothionein (MT) inducer, which plays an important role in protection against Cd toxicity. In this study, we investigated the protective effects of Zn against Cd toxicity in ECTs and explore the underlying mechanisms. ECTs were constructed from neonatal ventricular cells of wild-type (WT) mice and mice with global MT gene deletion (MT-KO). In WT-ECTs, Cd (5−20 μM) caused a dose-dependent toxicity that was detected within 8 h evidenced by suppressed beating, apoptosis, and LDH release; Zn (50−200 μM) dose-dependently induced MT expression in ECTs without causing ECT toxicity; co-treatment of ECT with Zn (50 µM) prevented Cd-induced toxicity. In MT-KO ECTs, Cd toxicity was enhanced; but unexpectedly, cotreatment with Zn provided partial protection against Cd toxicity. Furthermore, Cd, but not Zn, significantly activated Nrf2 and its downstream targets, including HO-1; inhibition of HO-1 by a specific HO-1 inhibitor, ZnPP (10 µM), significantly increased Cd-induced toxicity, but did not inhibit Zn protection against Cd injury, suggesting that Nrf2-mediated HO-1 activation was not required for Zn protective effect. Finally, the ability of Zn to reduce Cd uptake provided an additional MT-independent mechanism for reducing Cd toxicity. Thus, Zn exerts protective effects against Cd toxicity for murine ECTs that are partially MT-mediated. Further studies are required to translate these findings towards clinical trials.

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“…The percentage of viable cells was directly proportional to the optical density (at 540 nm) of purple colored formazan formed. Estimation of reactive oxygen species was carried out by dichlorofluorescin diacetate (DCFDA) method (Himedia, India) from 0 to 15 min soon after the treatment of areca nut extract as per earlier protocol [ 22 ]. Free radicals produced in cells on exposure of ANE was represented as percentage of fluorescent intensity at excitation (485 nm) and emission (527 nm) wavelength.…”

Section: Methodsmentioning

confidence: 99%

Regulation of Jun and Fos AP-1 transcription factors by JNK MAPKs signaling cascade in areca nut extract treated KB cells

Nagesh

Kumar²,

Kumar

et al. 2021

Biochemistry and Biophysics Reports

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The edible endosperm of Areca catechu is recognized as a potent carcinogenic agent either consumed alone or in combination with tobacco. Habitual chewing of areca nut leads to orally potential malignant disorders which are highly effective in malignant transformation and thereby lead to oral carcinogenesis. Human buccal epithelial KB carcinoma cells were used as an experimental cell system to inspect the mechanistic act of aqueous extract of areca nut on biochemical status and their implications on transcriptional activation of cancer signaling cascade that could possibly trigger numerous oncogenic players and finally decides the cells fate. Extract treated cells showed reduced viability with altered balance between oxidants and antioxidants which lead to redox status and which is known to distort various biological processes within the cell system. Results of RT-PCR demonstrated decreased expression of BCl2, cell cycle regulators along with Activator Protein −1 (AP-1) components. While Bax, p16 and p21 mRNAs showed increased expression in extract treated KB cells. Likewise, the translational levels of proliferation cell nuclear antigen (PCNA), tumor suppressor p53, retinoblastoma (Rb) and cyclin dependent kinase 4 (CDK4) were decreased along with AP-1 subunits (c-Jun/c-Fos) with increased protein levels of p21 in extract treated KB cells. Further, the downstream activation and regulation of AP-1 transcription factors could be through stress activated c-Jun – N terminal Kinase (JNK) Mitogen Activated Protein Kinases (MAPKs) which downregulated both Jun and Fos mRNA transcripts in areca nut extract exposed KB cells. Thus, outcome of the study provides insights into mechanistic path of pathogenesis of areca related disorders. Further, it could aid in designing new therapeutic modalities that specific targets these oncogenic players and help in disease management.

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Cadmium induces oxidative stress and apoptosis in lung epithelial cells

Cited by 44 publications

References 49 publications

Toxic metal exposure as a possible risk factor for COVID-19 and other respiratory infectious diseases

Toxic metal exposure as a possible risk factor for COVID-19 and other respiratory infectious diseases

Zinc protects against cadmium-induced toxicity in neonatal murine engineered cardiac tissues via metallothionein-dependent and independent mechanisms

Regulation of Jun and Fos AP-1 transcription factors by JNK MAPKs signaling cascade in areca nut extract treated KB cells

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