Acetaminophen toxicity in rat and mouse hepatocytes in vitro

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11150%2F17%3A10361701" target="_blank" >RIV/00216208:11150/17:10361701 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1080/01480545.2016.1255953" target="_blank" >http://dx.doi.org/10.1080/01480545.2016.1255953</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/01480545.2016.1255953" target="_blank" >10.1080/01480545.2016.1255953</a>

Result language

angličtina

Original language name

Acetaminophen toxicity in rat and mouse hepatocytes in vitro

Original language description

Context: Acetaminophen (APAP) hepatotoxicity is often studied in primary cultures of hepatocytes of various species, but there are only few works comparing interspecies differences in susceptibility of hepatocytes to APAP in vitro. Objectives: The aim of our work was to compare hepatotoxicity of APAP in rat and mouse hepatocytes in primary cultures. Materials and methods: Hepatocytes isolated from male Wistar rats and C57Bl/6J mice were exposed to APAP for up to 24 h. We determined lactate dehydrogenase (LDH) activity in culture medium, activity of cellular dehydrogenases (WST-1) and activity of caspases 3 in cell lysate as markers of cell damage/death. We assessed content of intracellular reduced glutathione, production of reactive oxygen species (ROS) and malondialdehyde (MDA). Respiration of digitonin-permeabilized hepatocytes was measured by high resolution respirometry and mitochondrial membrane potential (MMP) was visualized (JC-1). Results: APAP from concentrations of 2.5 and 0.75 mmol/L induced a decrease in viability of rat (p &lt; 0.001) and mouse (p &lt; 0.001) hepatocytes (WST-1), respectively. In contrast to rat hepatocytes, there was no activation of caspase-3 in mouse hepatocytes after APAP treatment. Earlier damage to plasma membrane and faster depletion of reduced glutathione were detected in mouse hepatocytes. Mouse hepatocytes showed increased glutamate + malate-driven respiration in state 4 and higher susceptibility of the outer mitochondrial membrane (OMM) to APAP-induced injury. Conclusion: APAP displayed dose-dependent toxicity in hepatocytes of both species. Mouse hepatocytes in primary culture however had approximately three-fold higher susceptibility to the toxic effect of APAP when compared to rat hepatocytes.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30105 - Physiology (including cytology)

Project

<a href="/en/project/NT14320" target="_blank" >NT14320: Study of a new mechanism of acetaminophen toxicity in liver and possibilities of therapy</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Drug and Chemical Toxicology

ISSN

0148-0545

e-ISSN

—

Volume of the periodical

40

Issue of the periodical within the volume

4

Country of publishing house

US - UNITED STATES

Number of pages

9

Pages from-to

448-456

UT code for WoS article

000406544200011

EID of the result in the Scopus database

2-s2.0-85006117471