Cytotoxicity and induction of protective mechanisms in HepG2 cells exposed to cadmium

Urani, Chiara; Melchioretto, Pasquale; Canevali, Carmen; Crosta, G

doi:10.1016/j.tiv.2005.06.011

Cited by 38 publications

(23 citation statements)

References 20 publications

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“…Unlike HSP60, HSP70 and HSP90 families belong to cytoplasmic chaperones that assist in a wide range of protein folding processes including refolding of misfolded and aggregated proteins in response to cellular stress (Bensaude et al, 1996;Söti and Csermely, 2000;Urani et al, 2005). In mammalian systems, Cd exposure has been found to induce stress proteins of 72 and 90·kDa in human keratinocytes and in fibroblasts, 70 and 90·kDa in primary rat hepatocytes, and 32, 72, 90 and 110·kDa in human melanoma cells (Bauman et al, 1993;Madden et al, 2002;Urani et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…In mammalian systems, Cd exposure has been found to induce stress proteins of 72 and 90·kDa in human keratinocytes and in fibroblasts, 70 and 90·kDa in primary rat hepatocytes, and 32, 72, 90 and 110·kDa in human melanoma cells (Bauman et al, 1993;Madden et al, 2002;Urani et al, 2005). In chick embryos, exposure to Cd enhanced de novo synthesis of HSP70, whereas HSP24 and HSP90 were unaffected (Papaconstantinou et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

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Effects of cadmium on cellular protein and glutathione synthesis and expression of stress proteins in eastern oysters, Crassostrea virginica Gmelin

Ivanina

Cherkasov

Sokolova

2008

Journal of Experimental Biology

134

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SUMMARYCadmium (Cd) is an important toxicant in estuarine and coastal environments that can strongly affect energy balance of aquatic organisms by increasing the organismʼs basal energy demand and reducing its aerobic capacity. Mechanisms of cadmiuminduced increase in basal metabolic costs are not well understood and may involve elevated detoxification costs due to the synthesis of cellular protective proteins and glutathione. We studied the short-term effects of cadmium exposure (4·h) on protein and glutathione (GSH) synthesis and expression of stress proteins (heat shock proteins HSP60, HSP70 and HSP90) and metallothioneins in isolated gill and hepatopancreas cells of the eastern oyster, Crassostrea virginica. Our study showed that exposure to cadmium resulted in a dose-dependent increase in the rate of protein synthesis in oyster cells, which reached 150% of the control at the highest tested Cd level (2000·mol·l -1 ). GSH synthesis was significantly inhibited by the highest Cd concentrations, especially in hepatopancreas, which resulted in a slight but significant decrease in the total GSH concentrations. Elevated protein synthesis was associated with the increased expression of metallothioneins and heat shock proteins. Interestingly, stress protein response differed considerably between gill and hepatopancreas cells. In hepatopancreas, expression of metallothionein mRNA (measured by real-time PCR) increased 2-8-fold in response to Cd exposure, whereas no significant increase in metallothionein expression was found in Cd-exposed gill cells. By contrast, HSP60 and HSP70 protein levels increased significantly in Cd-exposed gill cells (by 1.5-2-fold) but not in hepatopancreas. No change in HSP90 expression was detected in response to Cd exposure in oyster cells. These data indicate that metallothionein expression may provide sufficient protection against Cd-induced damage to intracellular proteins in hepatopancreas, alleviating the need for overexpression of molecular chaperones. By contrast, Cd detoxification mechanisms such as inducible metallothioneins and GSH appear to be insufficient to fully prevent protein damage in gill cells, thus necessitating induction of HSPs as a secondary line of cellular defense. Therefore, gills are likely to be among the most Cd-sensitive tissues in oysters, which may have important implications for impaired oxygen uptake contributing to energy misbalance and reduced aerobic scope in Cd-exposed oysters.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of cadmium on cellular protein and glutathione synthesis and expression of stress proteins in eastern oysters, Crassostrea virginica Gmelin

Ivanina

Cherkasov

Sokolova

2008

Journal of Experimental Biology

134

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“…Exposure to As, Cd and Pb cause adverse effects in various organs of the body (Tchounwou et al 2012) and their toxicity to the liver has been well characterized (Goering andBarber 2010, Tokar et al 2012). In vitro studies using HepG2 cells demonstrated the toxicity of As, Cd and Pb to liver cells (Tchounwou et al 2002, Urani et al 2005, Fotakis and Timbrell 2006, Yedjou et al 2010. The findings from our study also consistent with these reports, as all the metals were toxic to HepG2 cells.…”

Section: Discussionmentioning

confidence: 99%

“…The liver, an organ for biotransformation is one of the main target organs of exposed chemicals. B [a]P and metals accumulate in the liver followed by their absorption and cause toxicity to liver cells (Babich et al 1988, Chen et al 2002, Pourahmad et al 2005, Urani et al 2005, Shiizaki et al 2008. In this study, HepG2 (hepatocellular carcinoma) cell line was used to evaluate the interaction toxicity.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of interaction and combined toxicity of polyaromatic hydrocarbons (PAHs) and metals using human cell-based bioassays

Muthusamy¹

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Mixed contamination of polyaromatic hydrocarbons (PAHs) and metals are ubiquitous in the environment. Some of the individual PAHs are known as human carcinogens, and metals are associated with various systemic toxicity and cancers in humans. Although the individual toxicity of PAHs and metals are well documented, our present state of knowledge about the adverse health effects of these mixtures is very limited in terms of exposure associated toxicity in humans, the underlying mechanism of toxicity and predicting the toxicity of mixtures. Due to this, their risk assessment has been mostly carried out based on their individual toxicity data.This research work investigated the interaction and combined toxicity of four PAHs

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“…In published literature most studies have reported interaction of PAHs and metal/loids at binary combinations Lewińska et al, 2007;Evans et al, 2004;Mukherjee et al, 2004). However, in some recent publications the effects of PAHs and metal/loids interaction at ternary, quaternary 97 and up to seven compound mixtures on micronucleus formation (Cheng et al, 2015), Nrf2-antioxidant response pathway (Muthusamy et al, 2016b), oxidative stress (Muthusamy et al, 2016a) and cytotoxicity (Muthusamy et al, 2016c) following absorption and causing toxicity to liver cells Urani et al, 2005;Song et al, 2012;Babich et al, 1988). The HepG2 cell line has inherent metabolic capacity which is useful in determining toxicity of PAHs (Henkler et al, 2012), although their CYP expression has been reported to be lower in comparison to primary hepatocytes (Westerink et al, 2007;Gerets et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Health risk assessment of mixed contaminants: Interaction of metals on the uptake of polycyclic aromatic hydrocarbons in human liver cells

Lal¹

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A key area of uncertainty in human health risk assessment of chemical mixtures is the application of additivity of dose or effects, which may overestimate or underestimate the actual risk. In this PhD thesis, interaction effects among mixtures of benzo [a]pyrene (B[a]P), pyrene (Pyr), phenanthrene (Phe) and naphthalene (Nap) in the presence or absence of arsenic (As), cadmium (Cd), lead (Pb) is elucidated for bioaccessibility, uptake (surrogate bioavailability) and metabolism of PAHs in human systems using in vitro models. A simulated human digestion based on the use of an in vitro model (Unified BARGE Method) was used to quantify PAH bioaccessibility from exposure to contaminated soils, whereas a human liver hepatocellular (HepG2) cell line (surrogate liver) was used as an in vitro model to quantify uptake and metabolism of PAHs. This PhD To investigate bioaccessibility of PAHs, seven chemically-variant top soils were collected from background sites in Australia and were spiked with PAHs and aged up to 90 days.The UBM results suggest that the most significant interactions between PAHs and soil components controlling its bioaccessibility was completed by the first 7 days of ageing condition of this study. It is noted that there was a significant lower bioaccessibility of Data from pure solution study suggests that uptake of PAHs and in the presence of As, Cd, and Pb in HepG2 cells generally showed less than additive effects among binary, ternary and seven compound mixtures of B[a]P, Pyr, Phe and Nap. Notably, the % uptake of Phe in HepG2 cells was found to decrease significantly in the seven compound mixture (p < 0.05) which had As, Cd and Pb. Using UBM-extracted solutions, interaction effects on uptake of PAHs in HepG2 cells was found to be both additive and less than additive.Moreover, the % uptake data from UBM-extracted real soil samples showed a decrease in % uptake of B[a]P, Pyr, Phe and Nap by 0.7 %, 1.8 %, 0.4 % and 0.04 %, respectively when compared to their individual PAH % uptake in HepG2 cells from exposure to UBMextracted spiked soil samples.Results of bioaccessibility, uptake and metabolism of B[a]P, Pyr, Phe and Nap as individual compounds or mixtures in the presence or absence of As, Cd and Pb provide significant new understanding towards interaction effects of these compounds in the context of human health risk assessment. For assessment of soils contaminated with PAHs and metal/loids, it clarifies situations where additive effects can be expected rather than assuming additivity as a general rule in risk assessment of chemical mixtures.4

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Cytotoxicity and induction of protective mechanisms in HepG2 cells exposed to cadmium

Cited by 38 publications

References 20 publications

Effects of cadmium on cellular protein and glutathione synthesis and expression of stress proteins in eastern oysters, Crassostrea virginica Gmelin

Effects of cadmium on cellular protein and glutathione synthesis and expression of stress proteins in eastern oysters, Crassostrea virginica Gmelin

Evaluation of interaction and combined toxicity of polyaromatic hydrocarbons (PAHs) and metals using human cell-based bioassays

Health risk assessment of mixed contaminants: Interaction of metals on the uptake of polycyclic aromatic hydrocarbons in human liver cells

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