{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T20:32:26Z","timestamp":1769373146039,"version":"3.49.0"},"reference-count":78,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Agentura pro Zdravotnick\u00fd V\u00fdzkum"},{"name":"Czech Ministry of Health","award":["RVO-VFN64165\/2017"],"award-info":[{"award-number":["RVO-VFN64165\/2017"]}]},{"name":"BENEFICENTIA Stiftung"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:p>Observational epidemiological studies showed that mild hyperbilirubinemia has beneficial effects on the prevention of cardiovascular disease, type 2 diabetes mellitus, and metabolic syndrome. In mammals, bilirubin plays a major role as a potent antioxidant. Uridine 5\u2019\u2010diphospho\u2010glucuronosyl transferase (<jats:styled-content style=\"fixed-case\">UGT<\/jats:styled-content>)1A1 variants coding for bilirubin <jats:styled-content style=\"fixed-case\">UDP<\/jats:styled-content>\u2010glucuronosyl transferase resulting in mild hyperbilirubinemia (as in Gilbert syndrome (<jats:styled-content style=\"fixed-case\">GS<\/jats:styled-content>)) may confer a strong genetic advantage. Strategies to boost bioavailability of bilirubin or to mimic <jats:styled-content style=\"fixed-case\">GS<\/jats:styled-content> represent an attractive approach to prevent many oxidative stress and inflammation\u2010mediated diseases. Even a tiny, micromolar increase in serum bilirubin concentrations substantially decreases the risk of oxidative stress\u2013mediated diseases. There are several possible ways to achieve this, including lifestyle changes, changes in dietary patterns, regular physical activities, or use of chemical drug or of specific plant products either in the form of regular food items or nutraceuticals. Further basic and experimental research is required to fully uncover this promising therapeutic field.<\/jats:p>","DOI":"10.1002\/cpt.1341","type":"journal-article","created":{"date-parts":[[2018,12,27]],"date-time":"2018-12-27T09:38:56Z","timestamp":1545903536000},"page":"568-575","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Induction of Mild Hyperbilirubinemia: Hype or Real Therapeutic Opportunity?"],"prefix":"10.1111","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5318-0151","authenticated-orcid":false,"given":"Libor","family":"Vitek","sequence":"first","affiliation":[{"name":"Institute of Medical Biochemistry and Laboratory Diagnostics and 4th Department of Internal Medicine 1st Faculty of Medicine Charles University  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2865-2575","authenticated-orcid":false,"given":"Cristina","family":"Bellarosa","sequence":"additional","affiliation":[{"name":"Fondazione Italiana Fegato ONLUS AREA Science Park\u2010Basovizza  Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6596-7595","authenticated-orcid":false,"given":"Claudio","family":"Tiribelli","sequence":"additional","affiliation":[{"name":"Fondazione Italiana Fegato ONLUS AREA Science Park\u2010Basovizza  Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,3]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199511023331802"},{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/jphp.12053"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.116.015083"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2012.02576.x"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2261-12-16"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2005.04.008"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2016.07.004"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3029864"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2013.09.014"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-016-1835-3"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00396.2016"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.03.047"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(01)00601-3"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/15353702-0322805-29"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2012.00055"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2016.06.002"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.2337\/db14-0228"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2017.07.004"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.298.12.1398-b"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/obr.12229"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2017.12.021"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e318291fefe"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840400412"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018812021549"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.14.8170"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1258\/acb.2009.008203"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.42.2.172"},{"key":"e_1_2_11_28_1","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1093\/clinchem\/27.6.1140","article-title":"Fasting and gender (and altitude?) influence reference intervals for serum bilirubin in healthy adults [letter]","volume":"27","author":"White G.L.","year":"1981","journal-title":"Clin. Chem."},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2009.04.003"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2013.01.011"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/75.3.320"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1996.v111.pm8698202"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.17.5.335"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1177\/0003319714537111"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.5114\/biolsport.2017.63732"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0b013e3182357dd4"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2006.12.069"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-3485cmt"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2004.07.008"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12401"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2010.01.017"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0000000000000969"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.22.8.663"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567202613666161014161943"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1139\/Y07-077"},{"key":"e_1_2_11_46_1","first-page":"231a\u2010a","article-title":"Milk thistle natural polyphenols increase systemic as well as hepatic concentrations of bilirubin and decrease hepatic lipoperoxidation in mice","volume":"66","author":"Suk J.","year":"2017","journal-title":"Hepatology"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867324666170616110748"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2012.06.002"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.108.020503"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498254.2013.820006"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.8b00168"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498254.2011.623796"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328011d7c1"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000000970"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1159\/000091966"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2017.01.002"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.3816\/CCC.2007.n.015"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2005.01.011"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-006-9019-2"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.09.034"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498254.2010.505669"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.24.226"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498250601050420"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1250457"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.108.097279"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/135.5.1051"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1080\/01635589709514587"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-6915(01)00056-4"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1080\/15287399509531971"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6823-13-39"},{"key":"e_1_2_11_71_1","unstructured":"Dorresteijn M.D. Welzen M.E.B. der vanHoeven J.G. Pickkers P. Wagener F.A.G.T.D.&Smits P.Bilirubin infusion in human healthy volunteers. 7th International Congress on Heme Oxygenases and Related Enzymes Edinburgh UK 28 May \u20101 June 2012."},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201602525"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2017.06.014"},{"key":"e_1_2_11_74_1","first-page":"1","article-title":"Biotinylated bilirubin nanoparticles as a tumor microenvironment\u2010responsive drug delivery system for targeted cancer therapy","volume":"1800017","author":"Lee Y.","year":"2018","journal-title":"Adv. Sci."},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1177\/0963689717735112"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1097\/00029330-200803010-00024"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/4069167"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1665-2681(19)30891-9"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpt.1341","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.1341","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.1341","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.1341","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T13:29:24Z","timestamp":1699363764000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.1341"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3]]},"references-count":78,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,9]]}},"alternative-id":["10.1002\/cpt.1341"],"URL":"https:\/\/doi.org\/10.1002\/cpt.1341","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3]]},"assertion":[{"value":"2018-10-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}