Gender Differences in the Hepatotoxicity and Toxicokinetics of Emodin: The Potential Mechanisms Mediated by UGT2B7 and MRP2

Molecular Pharmaceutics
Lili WuLan Tang

Abstract

Emodin is a main anthraquinone compound which exists in Chinese traditional medicines including Polygonum multiflorum and Rhubarb. It is documented to have obvious liver and kidney toxicity. This study aims to (a) estimate gender differences of the hepatotoxicity and toxicokinetics in rats after oral administration of emodin (60 and 150 mg/kg/d) for a consecutive 28 days and (b) clarify relative mechanisms caused by glucuronidation and disposition. Hepatotoxicity was significantly higher in female rats than that in male rats, as evidenced by histopathological and biochemical tests. Similarly, the toxicokinetic profiles of emodin have time and gender differences, which could cause time and gender differences in hepatotoxicity. The metabolic and transcriptomics data of 55 human liver and 36 human kidney samples demonstrated that UDP-glucuronosyltransferase 2B7 (UGT2B7) was the predominant enzyme for emodin glucuronidation. A genome-wide association study (GWAS) identified that rs11726899 located within ∼50 kb of the transcript of UGT2B could significantly affect emodin metabolism. Knockdown of UGT2B7 in HepG2 cells significantly decreased emodin glucuronidation and increased cytotoxicity of emodin. The gene expression and protein...Continue Reading

References

Feb 17, 2001·Journal of Applied Toxicology : JAT·K H DiehlUNKNOWN European Federation of Pharmaceutical Industries Association and European Centre for the Validation of Alternative Methods
Oct 14, 2004·In Vitro Cellular & Developmental Biology. Animal·P F DehnT A Cumbo
Aug 2, 2005·Journal of Pediatric Gastroenterology and Nutrition·Bianca PanisPhilippe P R Rosias
May 16, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Akiko NakamuraTsuyoshi Yokoi
Mar 18, 2009·Bioinformatics·Cole TrapnellSteven L Salzberg
Apr 21, 2009·Journal of Ethnopharmacology·Jiabo WangCheng Jin
Sep 22, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Yan LiJin Ren
Jan 25, 2012·Journal of Applied Toxicology : JAT·Mostafa I WalyAbderrahim Nemmar
Mar 6, 2012·Nature Methods·Ben Langmead, Steven L Salzberg
May 23, 2012·Toxicology·Mei-Hui ChangWen-Hsiung Chan
Mar 19, 2013·The International Journal of Biochemistry & Cell Biology·Andrew RowlandPeter I Mackenzie
Dec 18, 2013·BMC Genomics·Shannon E EllisDan E Arking
Jan 8, 2014·Expert Opinion on Drug Metabolism & Toxicology·Li Di
May 27, 2014·Expert Review of Clinical Pharmacology·Flavia Franconi, Ilaria Campesi
May 27, 2014·Molecular Systems Biology·Anatole GhazalpourAldons J Lusis
Dec 3, 2014·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Cuifen WangLuyong Zhang
Feb 5, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Guillaume MargaillanChantal Guillemette
Mar 12, 2015·Drug Metabolism and Pharmacokinetics·Shingo OdaMiki Nakajima
May 4, 2015·European Heart Journal·Christoph VarenhorstUNKNOWN PLATO Investigators
May 15, 2015·Canadian Journal of Physiology and Pharmacology·Feng CaoHong Zhou
Jul 15, 2015·Cellular Oncology (Dordrecht)·Yaoxian WangGe Lou
Oct 30, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Michael A ZientekBill J Smith
Nov 12, 2015·Frontiers in Pharmacology·Can TuJia-Bo Wang
May 18, 2016·Phytotherapy Research : PTR·Xiaoxv DongJian Ni
Jul 5, 2016·Advanced Biomedical Research·Melva LouisaDin Syafruddin

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Citations

Dec 6, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Xue WangYoucai Zhang
Mar 4, 2020·Acta Pharmacologica Sinica·Tai RaoDong-Sheng Ou-Yang
Sep 26, 2020·Frontiers in Pharmacology·Qianqian LiYi Wang
Jun 20, 2020·European Journal of Pharmacology·Naihua HuYunxia Li
Apr 3, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Yitong LiuRobert L Sprando

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