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Currently, there is no simple, robust model used to assess and predict the porphyrogenicity of drugs and chemicals. Our aim was to develop a fluorescence\u2010based in vitro assay for this purpose. We studied four different hepatic cell culture models: HepG2 cells, LMH cells, 3D HepG2 organoids, and 3D organoids of primary liver cells from people without known disease [normal human controls]. We took advantage of the fluorescent properties of protoporphyrin IX [PP], the last intermediate of the heme biosynthesis pathway, performing fluorescence spectrometry to measure the intensity of fluorescence emitted by these cells treated with selected compounds of importance to patients with AHPs. Among the four cell culture models, the LMH cells produced the highest fluorescence readings, suggesting that these cells retain more robust heme biosynthesis enzymes or that the other cell models may have lost their inducibility of ALA synthase\u20101 [ALAS\u20101]. Allyl isopropyl acetamide [AIA], a known potent porphyrogen and inducer of ALAS\u20101, was used as a positive control to help predict porphyrogenicity for tested compounds. Among the tested compounds (acetaminophen, acetylsalicylic acid, \u03b2\u2010estradiol, hydroxychloroquine sulfate, alpha\u2010methyldopa, D (\u2010) norgestrel, phenobarbital, phenytoin, sulfamethoxazole, sulfisoxazole, sodium valproate, and valsartan), concentrations greater than 0.314\u00a0mM for norgestrel, phenobarbital, phenytoin, and sodium valproate produced fluorescence readings higher than the reading produced by the positive AIA control. Porphyrin accumulation was also measured by HPLC to confirm the validity of the assay. We conclude that LMH cell cultures in multi\u2010well plates are an inexpensive, robust, and simple system to predict the porphyrogenicity of existing or novel compounds that may exacerbate the AHPs.<\/jats:p>","DOI":"10.1002\/prp2.951","type":"journal-article","created":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T06:39:54Z","timestamp":1650523194000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Assessment of porphyrogenicity of drugs and chemicals in selected hepatic cell culture models through a fluorescence\u2010based screening assay"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4520-5849","authenticated-orcid":false,"given":"Christopher D.","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Section on Gastroenterology and Hepatology Wake Forest University School of Medicine  Winston\u2010Salem North Carolina 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7387-3230","authenticated-orcid":false,"given":"Herbert\u00a0L.","family":"Bonkovsky","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Section on Gastroenterology and Hepatology Wake Forest University School of Medicine  Winston\u2010Salem North Carolina 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