Systems Toxicology Approaches Reveal the Mechanisms of Hepatotoxicity Induced by Diosbulbin B in Male Mice.

Chemical Research in Toxicology
Hainan JiHua Li

Abstract

Diosbulbin B (DIOB) is an effective component of air potato yam with antitumor and anti-inflammatory activities, and it is the main toxic component leading to hepatotoxicity. However, the mechanism of its hepatotoxicity remains unclear. In this study, we aimed to systematically elucidate the molecular action of DIOB on liver metabolic function through systems toxicology approaches. C57BL/6 mice were orally treated with DIOB (10, 30, 60 mg/kg) for 28 days, and the liver metabonomics and histopathology, molecular docking, mRNA expression levels, and activities of enzymes were analyzed. The results illustrated that DIOB could affect fatty acid and glucose metabolism, block the TCA cycle, and DIOB also could disorder bile acid synthesis and transport and promote the occurrence of hyperbilirubinemia. In addition, DIOB increased Cyp3a11 expression in a dose-dependent manner. Thus, these results provide new insights into the mechanism of hepatotoxicity caused by DIOB.

References

Jun 24, 1989·Molecular and Cellular Biochemistry·J F Glatz, G J van der Vusse
Jun 24, 1989·Molecular and Cellular Biochemistry·R A Peeters, J H Veerkamp
Jan 1, 1997·Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists·R NiedermanS Kashket
Feb 27, 1998·Frontiers in Bioscience : a Journal and Virtual Library·J Y Chiang
Jun 9, 1999·Molecular Cell·H WangB M Forman
Oct 29, 2000·American Journal of Physiology. Endocrinology and Metabolism·J Y KimJ A Houmard
May 15, 2001·Biochemical and Biophysical Research Communications·G B MooreJ C Clapham
Jun 21, 2001·Chemical Research in Toxicology·F P Guengerich
Jan 29, 2002·Toxicological Sciences : an Official Journal of the Society of Toxicology·Hartmut JaeschkeJohn J Lemasters
Jun 18, 2002·The Journal of Pharmacology and Experimental Therapeutics·Masashi KitazawaAnumantha G Kanthasamy
Sep 13, 2002·Critical Care : the Official Journal of the Critical Care Forum·Fulvio IscraGianni Biolo
Jun 25, 2005·Journal of Hepatology·Christiane Pauli-MagnusPeter J Meier
Nov 26, 2005·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·M J Nunes de Paiva, M E Pereira Bastos de Siqueira
Oct 19, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shannon Reagan-ShawNihal Ahmad
Nov 27, 2007·Prostaglandins, Leukotrienes, and Essential Fatty Acids·Frédéric Calon, Greg Cole
Aug 1, 2008·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·S StahlM J Graham
Apr 11, 2009·World Journal of Gastroenterology : WJG·Maria-J Perez, Oscar Briz
Apr 29, 2009·Journal of Computational Chemistry·Garrett M MorrisArthur J Olson
Apr 24, 2010·Nuclear Receptor Signaling·Sean R PyperJanardan K Reddy
Jan 22, 2013·Drug Metabolism Reviews·Jeff L StaudingerWenqi Cui
May 31, 2013·International Immunopharmacology·Jinfeng MiaoLiuhai Zheng
Jul 31, 2013·Comprehensive Physiology·John Y L Chiang
Aug 21, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ryan E MorganHisham K Hamadeh
Oct 11, 2013·Human & Experimental Toxicology·Yibo MaZhengtao Wang
Feb 18, 2014·Nutrición hospitalaria·Thaís de Salgado RêgoGilson Teles Boaventura
Oct 23, 2014·Advanced Biomedical Research·Soheil Ashkani-EsfahaniAli Noorafshan
Apr 9, 2015·Archives of Toxicology·Weiwei LiJiang Zheng
Nov 12, 2016·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Ji-Zong JiangChang-Hong Wang

❮ 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.