PMID: 9443932Jan 28, 1998Paper

Interaction between iron metabolism and 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice with variants of the Ahr gene: a hepatic oxidative mechanism

Molecular Pharmacology
A G SmithM Toledano

Abstract

The binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) with the aryl hydrocarbon (AH) receptor and subsequent changes in gene expression have been studied intensively, but the mechanisms by which these lead to toxicity are unclear. We investigated the influence of iron, previously implicated in TCDD-induced hepatic porphyria, in mice with alleles of Ahr that encode receptors with varied affinity for TCDD. The administration of iron to Ahrb-1 C57BL/6J (AH-responsive) mice before a single dose of TCDD (75 micrograms/kg) markedly potentiated not only the hepatic porphyria but also general hepatocellular damage and elevation of plasma hepatic enzymes. The formation of hydroxylated and peroxylated derivatives of uroporphyrins formed from uroporphyrinogen and the induction of a mu-glutathione transferase (GST) were consistent with the operation of an oxidative mechanism. In a comparison of C57BL/6J mice with Ahrb-2 BALB/c (AH-responsive) and Ahrd SWR and DBA/2 (AH-nonresponsive) mice, iron overcame the weak hepatic porphyria and toxicity responses in BALB/c and SWR strains but not in DBA/2. CYP1A isoforms are strongly implicated in the mechanism of porphyria, but activities were lowered by 20-30% with iron treatment, and a compari...Continue Reading

References

Apr 1, 1991·Journal of Toxicology and Environmental Health·E S ShenJ R Olson
Sep 1, 1990·Bulletin of Environmental Contamination and Toxicology·Z Z WahbaS J Stohs
Sep 1, 1990·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·A G Smith, F De Matteis
Apr 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·E A Leibold, H N Munro
Jun 15, 1984·Toxicology and Applied Pharmacology·J B GreigA G Smith
Oct 1, 1981·Toxicology and Applied Pharmacology·K G JonesG D Sweeney
Oct 1, 1993·Pharmacogenetics·H I Swanson, C A Bradfield
Apr 1, 1993·The Biochemical Journal·A G Smith, J E Francis
Jan 15, 1996·Archives of Biochemistry and Biophysics·A GosiewskaB Peterkofsky
Mar 19, 1996·Proceedings of the National Academy of Sciences of the United States of America·J Y ParkB N Ames
Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·M W Hentze, L C Kühn
Sep 1, 1996·Toxicology and Applied Pharmacology·P M Fernandez-SalgueroF J Gonzalez
Sep 1, 1996·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·G CairoA Bernelli-Zazzera
Nov 8, 1996·Biochemical Pharmacology·D ConstantinA G Smith

❮ Previous
Next ❯

Citations

Jul 27, 2000·Food Additives and Contaminants·L S Birnbaum, J Tuomisto
Jul 4, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Wassana JamnongkanPuangrat Yongvanit
Feb 25, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Yan-Mei YangXu-Hong Song
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·John D PhillipsJames P Kushner
Mar 11, 2010·Antioxidants & Redox Signaling·Stefania RecalcatiGaetano Cairo
Mar 27, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Nadia GormanPeter R Sinclair
Jul 24, 2008·Dose-response : a Publication of International Hormesis Society·John F ReichardAlvaro Puga
Oct 29, 2008·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Kenzi NakanoShoichi Fujita
Dec 7, 2007·Expert Reviews in Molecular Medicine·Gaetano Cairo, Stefania Recalcati
Jul 13, 2014·Toxicological Sciences : an Official Journal of the Society of Toxicology·Keiko Aida-YasuokaChiharu Tohyama
May 3, 2012·Biochemistry Research International·Karine AndreauAida Bouharrour
Jan 27, 2010·Chemical Research in Toxicology·Andrew G Smith, George H Elder
Nov 18, 2000·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP· De Catabbi SCBL C de Viale
Jan 10, 2002·Toxicology and Applied Pharmacology·Albert P SenftHoward G Shertzer
Sep 6, 2002·Chemico-biological Interactions·Timothy P DaltonHoward G Shertzer
Jun 12, 2002·Free Radical Biology & Medicine·Gaetano CairoGiorgio Minotti
Aug 17, 2005·Molecular Aspects of Medicine·Susana Puntarulo
May 1, 2007·Toxicology and Applied Pharmacology·Nadia GormanPeter R Sinclair
Sep 24, 2009·Chemico-biological Interactions·Melissa L BarkerMichael R Franklin

❮ 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.