Metals, Hepatocytes, and Toxicology

Klaassen, Curtis D.; Stacey, Neill H.

doi:10.1016/b978-0-12-582870-3.50011-6

Cited by 6 publications

(2 citation statements)

References 128 publications

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“…Isolated hepatocytes are also widely used to study metal-induced toxicity [reviewed by Klaassen and Stacey (276)]. Some metals such as cadmium and mercury are not essential for life and are considered only from a toxicologic point of view, whereas other metals such as iron and copper are essential and only their excess is responsible for tissue damage.…”

Section: Characteristic Liver Lesions a Number Of Investigations Havmentioning

confidence: 99%

Liver Cell Models in in Vitro Toxicology

Guillouzo

1998

Environmental Health Perspectives

103

119

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In vitro liver preparations are increasingly used for the study of hepatotoxicity of chemicals. In recent years their actual advantages and limitations have been better defined. The cell models, slices, and mainly primary hepatocyte cultures, appear to be the most powerful in vitro systems, as liver-specific functions and responsiveness to inducers are retained either for a few days or several weeks depending on culture conditions. Maintenance of phase I and phase II xenobiotic metabolizing enzyme activities allows various chemical investigations to be performed, including determination of kinetic parameters, metabolic profile, interspecies comparison, inhibition and induction effects, and drug-drug interactions. In vitro liver cell models also have various applications in toxicology: screening of cytotoxic and genotoxic compounds, evaluation of chemoprotective agents, and determination of characteristic liver lesions and associated biochemical mechanisms induced by toxic compounds. Extrapolation of the results to the in vivo situation remains a matter of debate. Presently, the most convincing applications of liver cell models are the studies on different aspects of metabolism and mechanisms of toxicity. For the future, there is a need for better culture conditions and differentiated hepatocyte cell lines to overcome the limited availability of human liver tissues. In addition, strategies for in vitro analysis of potentially toxic chemicals must be better defined.

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Section: Characteristic Liver Lesions a Number Of Investigations Havmentioning

confidence: 99%

Liver Cell Models in in Vitro Toxicology

Guillouzo

1998

Environmental Health Perspectives

103

119

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“…Several studies have shown that cadmium is cytotoxic to isolated hepatocytes (276,277) and an approximate comparison of metal doses in vivo and in vitro indicates that cell death occurs at similar levels. Recent studies have shown that cadmium pretreatment exerts a protective effect against the genotoxicity of 2-acetylaminofluorene in cultured rat hepatocytes (278).…”

Section: However Survival and Metabolic Compe-mentioning

confidence: 99%

Liver cell models in in vitro toxicology.

Guillouzo

1998

Environ Health Perspect

300

125

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In vitro liver preparations are increasingly used for the study of hepatotoxicity of chemicals. In recent years their actual advantages and limitations have been better defined. The cell models, slices, and mainly primary hepatocyte cultures, appear to be the most powerful in vitro systems, as liver-specific functions and responsiveness to inducers are retained either for a few days or several weeks depending on culture conditions. Maintenance of phase and phase 11 xenobiotic metabolizing enzyme activities allows various chemical investigations to be performed, including determination of kinetic parameters, metabolic profile, interspecies comparison, inhibition and induction effects, and drug-drug interactions. In vitro liver cell models also have various applications in toxicology: screening of cytotoxic and genotoxic compounds, evaluation of chemoprotective agents, and determination of characteristic liver lesions and associated biochemical mechanisms induced by toxic compounds. Extrapolation of the results to the in vivo situation remains a matter of debate. Presently, the most convincing applications of liver cell models are the studies on different aspects of metabolism and mechanisms of toxicity. For the future, there is a need for better culture conditions and differentiated hepatocyte cell lines to overcome the limited availability of human liver tissues. In addition, strategies for in vitro analysis of potentially toxic chemicals must be better defined. Environ Health Perspect 106(Suppl 2):511-532 (1998). http.//ehpnetl.niehs.nih.gov/docs/1998/Suppl-2/51 1-532guillouzo/abstract.html

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Toxicity of heavy metals in cultured hepatocytes

Denizeau

Marion

Chtaib

et al. 1990

Enviro Toxic and Chemistry

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The cytotoxicity of three heavy metals that are representative environmental contaminants was investigated in primary cultures of rat hepatocytes. The cells were exposed to Cd, Ag or Hg and to mixtures comprised of Cd and either Ag or Hg at various concentrations. Incorporation of [3H]arginine ([3H]Arg) into proteins was used to monitor cytotoxic effects. In parallel, the uptake of metals by the cells was also determined. Concentration‐response profiles for each individual agent show that among the metals studied Cd is the most cytotoxic. This effect is not due to preferential uptake because the amounts of Ag and Hg accumulated by the cells (at low exposure concentrations) were similar to those of Cd. When Ag was used in combination with Cd, amino acid incorporation data showed no evidence of modulated toxicity. In contrast, when Hg was added with Cd, the results suggested the possibility of interaction: The reduction in incorporated [3H]Arg was more pronounced than that expected on the basis of individual responses. Measurement of metal uptake by the cells revealed that intracellular levels of Ag were comparable whether Cd was present or not. Similarly, the amount of Cd accumulated by the hepatocytes was not significantly affected by the presence of Ag or Hg. In conclusion, the present data describe the cytotoxicity of nonessential heavy metals in hepatocytes and their concomitant accumulation by the cells. It is therefore possible to examine one phenomenon in relation to the other. The results are further discussed in the light of the bioinorganic properties of the metals investigated.

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Metals, Hepatocytes, and Toxicology

Cited by 6 publications

References 128 publications

Liver Cell Models in in Vitro Toxicology

Liver Cell Models in in Vitro Toxicology

Liver cell models in in vitro toxicology.

Toxicity of heavy metals in cultured hepatocytes

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