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Acetaminophen Hepatotoxicity testing using 3D rat hepatocyte cultures
Author(s) -
Paliwal Vipin,
Clapham Margaret
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.609.14
Subject(s) - albumin , acetaminophen , hepatocyte , secretion , pharmacology , cell culture , in vitro , serum albumin , cytotoxicity , drug , cell , medicine , chemistry , biology , biochemistry , genetics
Animal models are currently used for drug development and testing but are expensive and often inaccurate. Monolayer (2D) cell culture models have been utilized due to lower cost, but have proven less reliable because they are unable to preserve the functionality of the liver in vitro . This study aimed to establish a more accurate and inexpensive pharmaceutical testing method that has reliability and reproducibility. H35 Rat Reuber hepatoma cells were grown in both two‐dimensional (2D) and three‐dimensional (3D) cell cultures. Cell cultures were treated with different concentrations of acetaminophen (APAP) and analyzed quantitatively for cytotoxicity using a Neutral Red Dye. Cell function was then assessed by quantification of albumin secretion using ELISA. Results showed that both 2D and 3D cultures declined in albumin production after 48 hrs treatment with 2.25 mM APAP treatment. After 72 hrs of treatment, 3D cells showed an 81.2% decline in albumin secretion even with a much lower dose of 0.15 mM APAP whereas 2D cells in fact increased albumin secretion slightly by 0.63% at this concentration. We conclude that when cells are grown in 3D cultures, an environment physiologically more similar to that of the liver, they have much higher sensitivity to acetaminophen hepatotoxicity. Support or Funding Information 1) National Science Foundation, 2) Milwaukee School of Engineering and 3) Medical College of Wisconsin