Mitochondrial dysfunction and delayed hepatotoxicity: another lesson from troglitazone.

Diabetologia
N L JulieG L Wilson

Abstract

Troglitazone was approved for treatment of type 2 diabetes mellitus, but by 2000 it had been removed from all world markets due to severe drug-induced liver injury. Even today, we still do not know how many patients sustained a long-term liver injury. No system is in place to acquire that knowledge. Regarding toxicity mechanisms, controversy persists as to which ones are class effects of thiazolidinediones (TZDs) and which are unique to troglitazone. This study aims to provide long-term outcome data and new insights on mechanisms of troglitazone-induced liver injury. This case series reports the liver injuries sustained by eleven type 2 diabetic patients treated with troglitazone between 1997 and 2000. Exhaustive review of medical records was performed for all patients. Long-term outcomes were available for all the non-fatal cases. A comprehensive literature review was also performed. Long-term liver injury progressing to cirrhosis was identified in seven patients. All eleven cases had liver injury patterns consistent with troglitazone toxicity. Analysis of these cases and of the experimental troglitazone toxicity data points to mitochondrial toxicity as a central factor. The general clinical patterns of mitochondrial hepatotox...Continue Reading

References

Aug 31, 1974·British Medical Journal·P J ToghillH L Matthews
Sep 1, 1982·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·H J Zimmerman, K G Ishak
Nov 1, 1982·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J H LewisE Rosenberg
Apr 1, 1995·Journal of Clinical Gastroenterology·Y SnirF Schlaeffer
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·S Lutsenko, M J Cooper
Jul 4, 1998·Annals of Internal Medicine·N GitlinH M Juarbe
Mar 6, 1999·Annals of Internal Medicine·S K Herrine, C Choudhary
Oct 9, 1999·Free Radical Biology & Medicine·S M BaileyC C Cunningham
Jan 22, 2000·Annals of Internal Medicine·J Al-SalmanM Mittal
Feb 24, 2000·The American Journal of Gastroenterology·A M BoothJ C Iezzoni
Apr 15, 2000·Annals of Internal Medicine·S Jagannath, R Rai
Jun 17, 2000·Diabetes Care·D S Bell, F Ovalle
Sep 16, 2000·Journal of Diabetes and Its Complications·H LiK M Klein
Apr 3, 2001·Digestive Diseases and Sciences·S H CaldwellR W von Borstel
Apr 3, 2001·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·D M BissellJ H Hoofnagle
Apr 12, 2001·Seminars in Liver Disease·D PessayreA Mansouri
Jan 10, 2002·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Antonio AcetiUNKNOWN LIVERHAART Group
Feb 28, 2002·The American Journal of Gastroenterology·Michael P Chase, Joseph C Yarze
Apr 12, 2002·Diabetic Medicine : a Journal of the British Diabetic Association·S NagasakaS Ishibashi
Apr 18, 2002·Journal of Clinical Gastroenterology·Manish DhawanGeorge Brodmerkel
May 23, 2002·Seminars in Liver Disease·Alan Bohan, James L Boyer
Jun 18, 2002·Alcoholism, Clinical and Experimental Research·Alan CahillAdrian Davies
Nov 19, 2002·Annals of Internal Medicine·Amar G PintoNaga Chalasani
Dec 25, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Shoichiro ShishidoMichio Sata
Mar 5, 2003·Age and Ageing·Amitalh SinghalShahid Anis Khan
Jun 17, 2003·Chemical Research in Toxicology·Martyn T Smith
Sep 17, 2003·The Journal of Toxicological Sciences·Urs A Boelsterli
Oct 18, 2003·Gastroenterology Clinics of North America·Lynette A Gillis, Ronald J Sokol
Oct 23, 2003·American Journal of Physiology. Endocrinology and Metabolism·Jerry R ColcaW Rodney Mathews
Feb 13, 2004·The New England Journal of Medicine·Kitt Falk PetersenGerald I Shulman
May 4, 2004·Annals of Neurology·Robert K Naviaux, Khue V Nguyen
May 29, 2004·The American Journal of Cardiology·Alawi A Alsheikh-Ali, Richard H Karas
Jun 30, 2004·Diabetes & Metabolism·B FromentyD Pessayre
Jan 13, 2005·Critical Care Medicine·Alexandra E Rätz BravoWolfgang Ummenhofer
Jun 4, 2005·Drug Metabolism Reviews·Shahrzad TafazoliPeter J O'Brien
Jun 21, 2005·Journal of Hepatology·Patrick F Chinnery, Salvatore DiMauro
Aug 2, 2005·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·E Björnsson, R Olsson
Aug 17, 2005·Current Medicinal Chemistry·David E Amacher
Jan 13, 2006·Mitochondrion·Karima BegricheBernard Fromenty

❮ Previous
Next ❯

Citations

Sep 11, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ryan E MorganHisham K Hamadeh
Jun 30, 2012·Journal of Gastroenterology and Hepatology·Chung-Wah WuJun Yu
Nov 13, 2012·Annual Review of Pharmacology and Toxicology·Jane P F Bai, Darrell R Abernethy
Jan 15, 2013·PPAR Research·Osamu KimuraTooru Shimosegawa
Dec 24, 2009·Drug Metabolism Reviews·Bruno Stieger
Mar 5, 2014·Expert Opinion on Drug Metabolism & Toxicology·Manuela de Lima Toccafondo Vieira, Carlos Alberto Tagliati
May 29, 2012·Expert Opinion on Drug Metabolism & Toxicology·Ajit DashBrian R Wamhoff
Sep 7, 2011·Drug Metabolism Reviews·Dominique PessayreAbdellah Mansouri
Jun 10, 2009·Expert Opinion on Drug Metabolism & Toxicology·Gordon Liss, James H Lewis
Nov 9, 2012·Expert Opinion on Drug Safety·Michele BortoliniBogdana Balas
Jul 30, 2009·Expert Opinion on Drug Metabolism & Toxicology·Ajit DashSteven R Tannenbaum
Mar 20, 2012·Journal of the Formosan Medical Association = Taiwan Yi Zhi·Chin-Hsiao Tseng
Feb 23, 2010·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Vijay K AgarwalUNKNOWN Drug-Induced Liver Injury Network
Mar 10, 2009·Diabetes/metabolism Research and Reviews
Apr 5, 2016·Proceedings of the National Academy of Sciences of the United States of America·Danny BavliYaakov Nahmias
May 17, 2015·International Journal of Toxicology·Thomas SteinbachNigel Greene
Feb 25, 2011·American Journal of Physiology. Cell Physiology·Barbara BrunmairClemens Fürnsinn
Oct 30, 2020·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Muluken Altaye AyzaDerbew Fikadu Berhe
Jul 22, 2021·APL Bioengineering·Erika Ferrari, Marco Rasponi

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.