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International Journal of Bioprinting                       Three-dimensional bioprinting in toxicological research
























            Figure 1. The main steps of the drug development process. Image created with BioRender.com.

            Table 1. CYP enzymes and their substrates investigated in ADME testing

                                                   Substrates of CYP enzymes
            CYP1A2            CYP2A6               CYP2B6                       CYP2C8             CYP2C9
            4-Aminobiphenyl   4-Nitroanisole       7-Benzyloxyresorufin         Amiodarone         Diclofenac
            7-Ethoxyresorufin  Coumarin            7-Ethoxy-4-trifluoro-methylcoumarin  Amodiaquine  Lauric acid
            7-Methoxyresorufin  Diethyl-nitrosamine  7-Ethoxy-coumarin          Arachidonic acid   Lornoxicam
            Caffeine          Indole               Bupropion                    Dibenzylfluorescein  Mefenamic acid
            Coumarin          Losigamone           Cinnarizine                  DMZ                Naproxen
            MeIQ              Methyl t-butyl ether  Deprenyl                    Fluvastatin        S-Flurbiprofen
            Melatonin         Nicotine             Loperamide                   Retinoic acid      S-Ibuprofen
            Naproxen          NNK                  Propofol                     Rosiglitazone      S-Warfarin
            Phenacetin        Quinoline            S-Mephenytoin                Zidovudine (AZT)   Tienilic acid
            Tacrine           SM-12052             Verapamil                    Zopiclone          Tolbutamide
             CYP2C19          CYP2D6               CYP2E1                        CYP3A4
            Clobazam          4-Methoxy-amphetamine  1,2-Dichloroethene         1-Nitropyrene
            Diazepam          Bufurolo             4-Nitrophenol                7-Benzyloxyresorufin
            DMZ               Bunitrolol           Chlorzoxazone                Coumarin
            Imipramine        Debrisoquine         Dapsone                      Erythromycin
            Omeprazole        Dextromethorphan     Dimethylnitrosamine          Felopidine
            Phenytoin         Imipramine           Ethanol                      Ketamine
            Proguanil         Metoprolol           Ethosuximide                 Midazolam
            R-Mephobarbital   MPTP                 Isoprene                     Nifedipine
            S-Mephenytoin     Propranolol          Paracetamol                  Ondansetron
            Ticlopidine       Thioridazine         Salicylic acid               Verapamil


            protein, hepatocyte growth factor (HGF), and Wnt ligands.   subsets of hepatoblasts exposed to signals near the portal
            During the formation of lobes and establishment of liver   mesenchyme generate cholangiocytes, while hepatoblasts
            bud, hepatoblasts can differentiate into hepatocytes or   located farther from the portal mesenchyme are closely
            cholangiocytes after lineage-commitment [15-17] . Recent   related to the hematopoietic cell. To support physiological
            research has shown that a single Lgr5-positive hepatoblast   functions, the adult liver should be maintained to
            can generate both hepatocytes and cholangiocytes in vivo.   support homeostasis. The ability of the liver to self-
            The fate of the hepatoblast is affected by signal transduction:   renew is typically 60 – 150  days in mice, slower than,


            Volume 9 Issue 2 (2023)                        199                      https://doi.org/10.18063/ijb.v9i2.663
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