Correlations of in vitro and in vivo hepatotoxicity for five haloalkanes

Tyson, Charles A.; Hawk-Prather, K.; Story, David L.; Gould, David

doi:10.1016/0041-008x(83)90105-9

Cited by 48 publications

(10 citation statements)

References 29 publications

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“…It is generally accepted that experiments are valid only if the background activity of control cells is ≤25% of total available intercellular activity. So, for control cells, the total intracellular enzyme content was determined after treatment of cells with Triton X-100 detergent to induce 100% lysis (Tyson et al, 1983).…”

Section: Assessment Of Hepatotoxic Activity In Vitromentioning

confidence: 99%

Hepatoprotective and antibacterial effects of extracts from Trichilia emetica Vahl. (Meliaceae)

Germanò

D’Angelo

Sanogo

et al. 2005

Journal of Ethnopharmacology

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Section: Assessment Of Hepatotoxic Activity In Vitromentioning

confidence: 99%

Hepatoprotective and antibacterial effects of extracts from Trichilia emetica Vahl. (Meliaceae)

Germanò

D’Angelo

Sanogo

et al. 2005

Journal of Ethnopharmacology

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“…A convenient end-point for cytotoxicity assessment in hepatoeytes is the determination of the leakage of lactate dehydrogenase (LDH) from damaged hepatocytes into the culture medium, generally referred to as LDH release (Mitchell and Aeosta, 1981;McQueen and Williams, 1982;Tyson et al, 1983). During a given incubation time, the concentration of a test chemical required to release 50% of the total intracellular LDH (50% inhibitory concentration or ICs0) is a useful parameter for comparing the toxicities of drugs and other chemicals (Ekwall and Acosta, 1982).…”

Section: Introductionmentioning

confidence: 99%

Intracellular lactate dehydrogenase concentration as an index of cytotoxicity in rat hepatocyte primary culture

1988

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In searching for a reliable index for cytotoxicity testing in rat hepatocyte primary culture, lactate dehydrogenase (LDH) concentrations in lysates of attached hepatocytes and LDH released into the culture medium were compared under conditions of exposure to various dosages of sodium chloride, sodium salicylate, R-warfarin, acetaminophen, phenylbutazone, and furosemide (frusemide). The amount of intracellular LDH was assessed by inducing the cells to release the enzyme with 0.1% Triton X-100. The induced LDH leakage was completed in 1 hr and the LDH activity was stable in storage at 10 degrees for 2 weeks. We found that intracellular LDH is a direct indicator of the number of viable hepatocytes in contrast to the LDH released, because released LDH does not account for the significant number of cells detached from monolayer but which are not leaky, during the 6-hr test period. Based on IC50 values (50% inhibitory concentration), the relative cytotoxicities are R-warfarin greater than phenylbutazone greater than furosemide greater than acetaminophen greater than sodium salicylate greater than sodium chloride.

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“…33 In addition, primary hepatocytes have been utilized as an in vitro model for determining hepatotoxicity and have shown strong correlation to in vivo hepatotoxicity. [34][35][36] In spite of the acceptance of hepatocytes in pharmaceutical research, they have had minimal use for short-term suspension assays or multi-day culturing protocols in HTS studies. Human hepatocytes in suspension cultures lasting several hours have been utilized in 96-well and 384-well formats for determining the metabolic clearance of drugs.…”

Section: Introductionmentioning

confidence: 99%

Assessment of Compound Hepatotoxicity Using Human Plateable Cryopreserved Hepatocytes in a 1536-Well-Plate Format

Moeller¹,

Shukla

Xia

2012

ASSAY and Drug Development Technologies

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Hepatotoxicity is a major concern for both drug development and toxicological evaluation of environmental chemicals. The assessment of compound-induced hepatotoxicity has traditionally relied on in vivo testing; however, it is being replaced by human in vitro models due to an emphasis on the reduction of animal testing and species-specific differences. Since most cell lines and hybridomas lack the full complement of enzymes at physiological levels found in the liver, primary hepatocytes are the gold standard to study liver toxicities in vitro due to the retention of most of their in vivo activities. Here, we optimized a cell viability assay using plateable cryopreserved human hepatocytes in a 1536-well-plate format. The assay was validated by deriving inhibitory concentration at 50% values for 12 known compounds, including tamoxifen, staurosporine, and phenylmercuric acetate, with regard to hepatotoxicity and general cytotoxicity using multiple hepatocyte donors. The assay performed well, and the cytotoxicity of these compounds was confirmed in comparison to HepG2 cells. This is the first study to report the reliability of using plateable cryopreserved human hepatocytes for cytotoxicity studies in a 1536-well-plate format. These results suggest that plateable cryopreserved human hepatocytes can be scaled up for screening a large compound library and may be amenable to other hepatocytic assays such as metabolic or drug safety studies.

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Correlations of in vitro and in vivo hepatotoxicity for five haloalkanes

Cited by 48 publications

References 29 publications

Hepatoprotective and antibacterial effects of extracts from Trichilia emetica Vahl. (Meliaceae)

Hepatoprotective and antibacterial effects of extracts from Trichilia emetica Vahl. (Meliaceae)

Intracellular lactate dehydrogenase concentration as an index of cytotoxicity in rat hepatocyte primary culture

Assessment of Compound Hepatotoxicity Using Human Plateable Cryopreserved Hepatocytes in a 1536-Well-Plate Format

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