References
Aono S, Adachi Y, Uyama E, Yamada Y, Keino H, Nanno T, Koiwai O, Sato H (1995) Analysis of genes for bilirubin UDP-glucuronosyltransferase in Gilbert’s syndrome. Lancet 345:958–959
Bell CC, Hendriks DF, Moro SM, Ellis E, Walsh J, Renblom A, Fredriksson Puigvert L, Dankers AC, Jacobs F, Snoeys J, Sison-Young RL, Jenkins RE, Nordling A, Mkrtchian S, Park BK, Kitteringham NR, Goldring CE, Lauschke VM, Ingelman-Sundberg M (2016) Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease. Sci Rep 6:25187
Bosma PJ, Chowdhury JR, Bakker C, Gantla S, de Boer A, Oostra BA, Lindhout D, Tytgat GN, Jansen PL, Oude Elferink RP et al (1995) The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert’s syndrome. N Engl J Med 333:1171–1175
Brandon EF, Raap CD, Meijerman I, Beijnen JH, Schellens JH (2003) An update on in vitro test methods in human hepatic drug biotransformation research: pros and cons. Toxicol Appl Pharmacol 189:233–246
Dalvie D, Obach RS, Kang P, Prakash C, Loi CM, Hurst S, Nedderman A, Goulet L, Smith E, Bu HZ, Smith DA (2009) Assessment of three human in vitro systems in the generation of major human excretory and circulating metabolites. Chem Res Toxicol 22:357–368
Erlinger S, Arias IM, Dhumeaux D (2014) Inherited disorders of bilirubin transport and conjugation: new insights into molecular mechanisms and consequences. Gastroenterology 146:1625–1638
Gomez-Lechon MJ, Donato MT, Castell JV, Jover R (2003) Human hepatocytes as a tool for studying toxicity and drug metabolism. Curr Drug Metab 4:292–312
Guo L, Dial S, Shi L, Branham W, Liu J, Fang JL, Green B, Deng H, Kaput J, Ning B (2011) Similarities and differences in the expression of drug-metabolizing enzymes between human hepatic cell lines and primary human hepatocytes. Drug Metab Dispos 39:528–538
Hewitt NJ, Lechon MJ, Houston JB, Hallifax D, Brown HS, Maurel P, Kenna JG, Gustavsson L, Lohmann C, Skonberg C, Guillouzo A, Tuschl G, Li AP, LeCluyse E, Groothuis GM, Hengstler JG (2007) Primary hepatocytes: current understanding of the regulation of metabolic enzymes and transporter proteins, and pharmaceutical practice for the use of hepatocytes in metabolism, enzyme induction, transporter, clearance, and hepatotoxicity studies. Drug Metab Rev 39:159–234
Ikeda Y, Jomura T, Horiuchi U, Saeki J, Yoshimoto K, Ikeya T, Nagasaki Y (2012) Long-term survival and functional maintenance of hepatocytes by using a microfabricated cell array. Colloids Surf B: Biointerfaces 97:97–100
Jemnitz K, Lengyel G, Vereczkey L (2002) In vitro induction of bilirubin conjugation in primary rat hepatocyte culture. Biochem Biophys Res Commun 291:29–33
Kadakol A, Ghosh SS, Sappal BS, Sharma G, Chowdhury JR, Chowdhury NR (2000) Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype. Hum Mutat 16:297–306
Kobayashi K, Yoshida A, Ejiri Y, Takagi S, Mimura H, Hosoda M, Matsuura T, Chiba K (2012) Increased expression of drug-metabolizing enzymes in human hepatocarcinoma FLC-4 cells cultured on micro-space cell culture plates. Drug Metab Pharmacokinet 27:478–485
Lauschke VM, Shafagh RZ, Hendriks DFG, Ingelman-Sundberg M (2019) 3D primary hepatocyte culture Systems for Analyses of liver diseases, drug metabolism, and toxicity: emerging culture paradigms and applications. Biotechnol J 14:e1800347
Lengyel G, Veres Z, Szabo P, Vereczkey L, Jemnitz K (2005) Canalicular and sinusoidal disposition of bilirubin mono- and diglucuronides in sandwich-cultured human and rat primary hepatocytes. Drug Metab Dispos 33:1355–1360
Ma G, Lin J, Cai W, Tan B, Xiang X, Zhang Y, Zhang P (2014) Simultaneous determination of bilirubin and its glucuronides in liver microsomes and recombinant UGT1A1 enzyme incubation systems by HPLC method and its application to bilirubin glucuronidation studies. J Pharm Biomed Anal 92:149–159
Ohkura T, Ohta K, Nagao T, Kusumoto K, Koeda A, Ueda T, Jomura T, Ikeya T, Ozeki E, Wada K, Naitoh K, Inoue Y, Takahashi N, Iwai H, Arakawa H, Ogihara T (2014) Evaluation of human hepatocytes cultured by three-dimensional spheroid systems for drug metabolism. Drug Metab Pharmacokinet 29:373–378
Ramaiahgari SC, den Braver MW, Herpers B, Terpstra V, Commandeur JN, van de Water B, Price LS (2014) A 3D in vitro model of differentiated HepG2 cell spheroids with improved liver-like properties for repeated dose high-throughput toxicity studies. Arch Toxicol 88:1083–1095
Soars MG, Riley RJ, Findlay KA, Coffey MJ, Burchell B (2001) Evidence for significant differences in microsomal drug glucuronidation by canine and human liver and kidney. Drug Metab Dispos 29:121–126
Sticova E, Jirsa M (2013) New insights in bilirubin metabolism and their clinical implications. World J Gastroenterol 19:6398–6407
Takahashi Y, Hori Y, Yamamoto T, Urashima T, Ohara Y, Tanaka H (2015) 3D spheroid cultures improve the metabolic gene expression profiles of HepaRG cells. Biosci Rep 35
Troberg J, Jarvinen E, Muniz M, Sneitz N, Mosorin J, Hagstrom M, Finel M (2015) Dog UDP-glucuronosyltransferase enzymes of subfamily 1A: cloning, expression, and activity. Drug Metab Dispos 43:107–118
Wang Q, Dai Z, Wen B, Ma S, Zhang Y (2015) Estimating the differences of UGT1A1 activity in recombinant UGT1A1 enzyme, human liver Microsomes and rat liver microsome incubation Systems in Vitro. Biol Pharm Bull 38:1910–1917
Westerink WM, Schoonen WG (2007) Phase II enzyme levels in HepG2 cells and cryopreserved primary human hepatocytes and their induction in HepG2 cells. Toxicol in Vitro 21:1592–1602
Wilkening S, Stahl F, Bader A (2003) Comparison of primary human hepatocytes and hepatoma cell line Hepg2 with regard to their biotransformation properties. Drug Metab Dispos 31:1035–1042
Funding
This study was supported in part by the financial support of the Research Clusters program of Tokushima University (No. 1701001).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Editor: Tetsuji Okamoto
Rights and permissions
About this article
Cite this article
Hirano, T., Hirata, M., Fujimoto, S. et al. Comparative analysis of bilirubin glucuronidation activity in 2D- and 3D-cultured human hepatocellular carcinoma HepG2 cells. In Vitro Cell.Dev.Biol.-Animal 56, 277–280 (2020). https://doi.org/10.1007/s11626-020-00451-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11626-020-00451-8