Precision-cut tissue slices: Applications in pharmacology and toxicology

Parrish, Alan R.; Gandolfi, A. Jay; Brendel, Klaus

doi:10.1016/0024-3205(95)02176-j

Cited by 228 publications

(133 citation statements)

References 107 publications

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“…Introduced in the early 1980s (13), precision-cut tissue-slice culture has attracted interest as a test system with which to examine drug metabolism in vitro (14)(15)(16)(17). Recently the adrenal medulla has been examined with this method (18,19).…”

mentioning

confidence: 99%

Irreversible Binding and Adrenocorticolytic Activity of the DDT Metabolite 3-Methylsulfonyl-DDE Examined in Tissue-Slice Culture

Lindhe¹,

Lund²,

Bergman³

et al. 2001

Environ Health Perspect

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mentioning

confidence: 99%

Irreversible Binding and Adrenocorticolytic Activity of the DDT Metabolite 3-Methylsulfonyl-DDE Examined in Tissue-Slice Culture

Lindhe¹,

Lund²,

Bergman³

et al. 2001

Environ Health Perspect

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“…Dating back to 1923, liver slices were rst prepared by Otto Warburg (35). The liver-slice models using precision-cut slices that were established in past years (43,75) retain tissue organization and cell-to-cell matrix interactions such as perfused organs. However, bile ow and functional parameters such as portal ow cannot be analyzed.…”

Section: Precision Cut Liver Slicesmentioning

confidence: 99%

In Vitro Models to Study Hepatotoxicity

Groneberg¹,

Große-Siestrup

Fischer³

2002

Toxicol Pathol

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Drug discovery and developmen t consists of a series of processes starting with the demonstration of pharmacologica l effects in experimental cell and animal models and ending with drug safety and ef cacy studies in patients. A main limitation is often the unacceptabl e level of toxicity with the liver as the primary target organ. Therefore, approache s to study hepatic toxicity in the early phase of drug discovery represent an important step towards rational drug development . A variety of in vitro liver models have been developed in the past years. Next to their use in drug development , they can also be applied to study environmenta l toxins and their hepatotoxicity. The 3 main approache s are ex vivo isolated and perfused organ models, precision-cut liver slices and cell culture models. Although the advantage of whole organ perfusions is based on the assessment of physiologic parameters such as bile production and morphologi c parameters such as tissue histology, cell culture models can be ef ciently used to assess cellular metabolism, cytotoxicity and genotoxicit y. The advantage of precision-cut liver slices is based on the juxtaposition of cellular assays and tissue morpholog y. None of these models can be compared as they all focus on different elds of hepatoxicolog y. For the future, the ideal setup for testing the hepatic toxicity of a new compoun d could of primary studies in cell or slice cultures to assess cellular effects and secondary studies using ex vivo perfused organs to examine gross organ function parameters and histology.

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“…This would in turn allow parenchymal cells to metabolize toxicants in a familiar local environment. In addition to the benefits of architecture maintenance, precision-cut slices allow for: no confounding issue of systemic influences as seen in vivo, rapid generation of reproducible tissue slices under minimally traumatic conditions, and the slice thickness and diameter can be optimized for efficient gas and nutrient exchange (16). The resultant integrated response to the toxicant may reflect events occurring in vivo.…”

Section: Morphological Evaluation-histology and Micrographymentioning

confidence: 99%

Correlation Between In Vivo and In Vitro Pulmonary Responses to Jet Propulsion Fuel-8 Using Precision-Cut Lung Slices and a Dynamic Organ Culture System

2003

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In tissue slice models, interactions between the heterogeneous cell types comprising the lung parenchyma are maintained thus providing a controlled system for the study of pulmonary toxicology in vitro. However, validation of the model in vitro system must be affirmed. Previous reports, in in vivo systems, have demonstrated that Clara cells and alveolar type II cells are the targets following inhalation of JP-8 jet fuel. We have utilized the lung slice model to determine if cellular targets are similar following in vitro exposure to JP-8. Agar-filled adult rat lung explants were cored and precision cut, using the Brendel/Vitron tissue slicer. Slices were cultured on titanium screens located as half-cylinders in cylindrical Teflon cradles that were loaded into standard scintillation vials and incubated at 37 • C. Slices were exposed to JP-8 jet fuel (0.5 mg/ml, 1.0 mg/ml, and 1.5 mg/ml in medium) for up to 24 hours. We determined ATP content using a luciferin-luciferase bioluminescent assay. No significant difference was found between the JP-8 jet fuel doses or time points, when compared to controls. Results were correlated with structural alterations following aerosol inhalation of JP-8. As a general observation, ultrastructural evaluation of alveolar type II cells revealed an apparent increase in the number and size of surfactant secreting lamellar bodies that was JP-8 jet fuel-dose dependent. These results are similar to those observed following aerosol inhalation exposure. Thus, the lung tissue slice model appears to mimic in vivo effects of JP-8 and therefore is a useful model system for studying the mechanisms of lung injury following JP-8 exposure.

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Precision-cut tissue slices: Applications in pharmacology and toxicology

Cited by 228 publications

References 107 publications

Irreversible Binding and Adrenocorticolytic Activity of the DDT Metabolite 3-Methylsulfonyl-DDE Examined in Tissue-Slice Culture

Irreversible Binding and Adrenocorticolytic Activity of the DDT Metabolite 3-Methylsulfonyl-DDE Examined in Tissue-Slice Culture

In Vitro Models to Study Hepatotoxicity

Correlation Between In Vivo and In Vitro Pulmonary Responses to Jet Propulsion Fuel-8 Using Precision-Cut Lung Slices and a Dynamic Organ Culture System

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