Elucidation of the Molecular Mechanisms Underlying Sorafenib-Induced Hepatotoxicity

Oxidative Medicine and Cellular Longevity
Abdullah F AlAsmariAli A Alshamrani

Abstract

Sorafenib is a small, orally-active multikinase inhibitor that is most frequently used for the management of renal cell carcinoma, hepatocellular carcinoma, and radioactive iodine-resistant thyroid carcinoma. However, recent reports have associated sorafenib with hepatotoxicity that can limit its clinical application, although the mechanism of hepatotoxicity is still to be elucidated. Thus, our study was designed to explore the molecular mechanisms underlying sorafenib-induced hepatotoxicity in an in vivo model. Twenty male adult Wistar rats were randomly placed into two groups; the first group received an oral dose of normal saline (vehicle), and the second received sorafenib (30 mg/kg) once daily for twenty-one consecutive days. After twenty-one days, liver tissues and blood samples were used for gene expression, protein expression, and biochemical analysis. Sorafenib treatment resulted in markedly increased levels of alanine aminotransferase and alkaline phosphatase, which indicate the presence of liver damage. Additionally, sorafenib administration induced the inflammatory and oxidative stress marker NF-κB-p65, while antioxidant enzymes were attenuated. Moreover, sorafenib caused upregulation of both gene and protein for th...Continue Reading

References

Jan 1, 1992·Free Radical Research Communications·R SchreckP A Baeuerle
Jan 1, 1997·British Medical Bulletin·A H Wyllie
Dec 9, 1997·Cell·G S Salvesen, V M Dixit
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jun 7, 2003·The Journal of Infectious Diseases·Edward Abraham
Feb 7, 2006·European Journal of Pharmacology·R PratibhaChitra Y Dhume
Nov 15, 2006·Annals of Surgical Oncology·Neeltje SteeghsHans Gelderblom
Sep 14, 2007·Chemico-biological Interactions·Neife Aparecida Guinaim dos SantosAntonio Cardozo dos Santos
Feb 20, 2008·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Yingjun LiaoHao Tang
Jul 10, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Dirk Strumberg
Dec 17, 2009·Leukemia & Lymphoma·Tamar TadmorAaron Polliack
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Dec 22, 2012·Toxicology Mechanisms and Methods·Summya RashidSarwat Sultana
Feb 15, 2013·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Jun YanJian Zhou
Dec 17, 2014·Basic & Clinical Pharmacology & Toxicology·Ye LiXian-Jun Qu
Apr 24, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jessica LoTerence Kin Wah Lee
Sep 26, 2015·Cancers·Tarik Regad
Oct 1, 2015·Hepatology International·Rosaria SpinellaRajiv Jalan
Apr 5, 2016·Drug Design, Development and Therapy·Fabián Pitoia, Fernando Jerkovich
May 27, 2016·Journal of Basic and Clinical Physiology and Pharmacology·Thangaiyan RadhigaKodukkur Viswanathan Pugalendi
Oct 23, 2016·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Neehar D ParikhVahakn Shahinian
Dec 4, 2016·BMC Complementary and Alternative Medicine·Mohammad RaishMushtaq Ahmad Ansari
Dec 13, 2016·The Biochemical Journal·Philip NewsholmePaulo Ivo Homem de Bittencourt
May 31, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Phatchawan ArjinajarnAnusorn Lungkaphin
Oct 14, 2017·American Journal of Physiology. Gastrointestinal and Liver Physiology·Ricard MasiaGary Yellen
Feb 20, 2018·Molecular Cancer·Wagner Ricardo MontorFabiana Henriques Machado de Melo
Oct 3, 2018·Research in Pharmaceutical Sciences·Maedeh HamzehFereshteh Talebpour Amiri
Nov 9, 2018·Frontiers in Pharmacology·Bee Ling TanHeshu Sulaiman Rahman
Mar 15, 2019·Journal of Hematology & Oncology·Shuang QinKongming Wu
Aug 23, 2019·International Journal of Molecular Sciences·Antje GartenMelanie Penke
Oct 23, 2019·Toxicology and Applied Pharmacology·Hao YanPeihua Luo

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Citations

Nov 1, 2020·Basic & Clinical Pharmacology & Toxicology·Raja David Isac Evangeline BreetaDevarajan David Wilson
Feb 8, 2022·Biological Trace Element Research·Can-Can ZhouDong-Jie Li

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