Publication detail

Steatotic rat hepatocytes in primary culture are more susceptible to the acute toxic effect of acetaminophen

Year: 2012

Type of publication: článek v odborném periodiku

Name of source: Physiological Research

Publisher name: Fyziologický ústav AV ČR

Place: Praha

Page from-to: S93-S101

Titles:

Language	Name	Abstract	Keywords
cze	Steatotické potkaní hepatocyty v primární kultuře jsou citlivější k akutnímu toxickému působení acetaminofenu	Předávkování acetaminofenem je vedoucí příčina léky zapříčiněného akutního jaterního selhání. Nealkoholové ztukovatění jater je nejčastější příčinou chronického ztukovatění jater. Cílem naší práce bylo porovnat toxický vliv APAP u intaktních hepatocytů a u hepatocytů z steatotických potkanů.	Steatóza; acetaminofen; hepatocyty
eng	Steatotic rat hepatocytes in primary culture are more susceptible to the acute toxic effect of acetaminophen	Acetaminophen (APAP) overdose is the most common cause of acute liver failure in humans. Non-alcoholic fatty liver disease is the most frequent chronic liver disease in developed countries. The aim of our work was to compare the effect of APAP on intact rat hepatocytes and hepatocytes isolated from steatotic liver in primary cultures. Male Wistar rats were fed with standard diet (10 % energy from fat) and high-fat diet (71 % energy from fat) for 6 weeks and then hepatocytes were isolated. After cell attachment, APAP (1; 2.5; 3.75 and 5 mM) was added to culture media (William´s E medium) and hepatocytes were cultured forup to 24 hours. APAP caused more severe dose-dependent damage of steatotic hepatocytes as documented by increased release of lactate dehydrogenase (LDH) and LDH leakage, decreased activity of cellular dehydrogenases (WST-1 test) and reduced albumin production. Intact steatotic hepatocytes contained lower amount of reduced glutathione (GSH). Treatment with APAP (1 and 2.5 mmol/l) caused more pronounced decrease in GSH in steatotic hepatocytes. ROS (reactive oxygen species) formation after 24-hour incubation was significantly higher in fatty hepatocytes using APAP at concentration of 3.75 and 5 mmol/l. Interleukin 6 (IL-6) production was elevated in 2.5 mM APAP-treated nonsteatotic and steatotic hepatocyte cultures at 8 hours, compared to appropriate controls. In conclusions, our results indicate that steatotic hepatocytes exert higher sensitivity to the toxic action of APAP. This sensitivity may be caused by lower content of GSH in intact steatotic hepatocytes and by more pronounced APAPinduced decrease in intracellular concentration of GSH.	Steatosis; acetaminophen; hepatocytes

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