Prediction of the metabolic clearance of benzophenone-2, and its interaction with isoeugenol and coumarin using cryopreserved human hepatocytes in primary culture

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association
G de SousaR Rahmani

Abstract

Benzophenone-2 (BP2) is widely used as a UV screen in both industrial products and cosmetic formulations, where it is frequently found associated with fragrance compounds, such as isoeugenol and coumarin. BP2 is now recognized as an endocrine disruptor, but to date, no information has been reported on its fate in humans. The intrinsic clearance (Clint) and metabolic interactions of BP2 were explored using cryopreserved human hepatocytes in primary cultures. In vitro kinetic experiments were performed to estimate the Michaelis-Menten parameters. The substrate depletion method demonstrated that isoeugenol was cleared more rapidly than BP2 or coumarin (Clint = 259, 94.7 and 0.40 μl/min/10(6) cells respectively). This vitro model was also used to study the metabolic interactions between BP2 and isoeugenol and coumarin. Coumarin exerted no effects on either isoeugenol or BP2 metabolism, because of its independent metabolic pathway (CYP2A6). Isoeugenol appeared to be a potent competitive substrate inhibitor of BP2 metabolism, equivalent to the specific UGT1A1 substrate: estradiol. Despite the fact that inhibition of UGT by xenobiotics is not usually considered to be a major concern, the involvement of UGT1A1 in BP2 metabolism may hav...Continue Reading

References

Jul 27, 1999·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·B G Lake
Mar 22, 2002·The Journal of Pharmacology and Experimental Therapeutics·M G SoarsR J Riley
Nov 7, 2002·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·D A BadgerI G Sipes
Apr 16, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yuichiro WatanabeTsuyoshi Yokoi
Aug 21, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Hannah M Jones, J Brian Houston
Oct 6, 2005·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·S P FelterG P Daston
Oct 10, 2006·Toxicology and Applied Pharmacology·Petra Y Kunz, Karl Fent
Feb 3, 2007·Chemico-biological Interactions·Albert P Li
Jul 25, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·R K Kuester, I G Sipes
Aug 29, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Hayley S BrownJ Brian Houston
Sep 25, 2007·Toxicology and Applied Pharmacology·Christin J WeisbrodKarl Fent
Feb 5, 2008·Toxicology·Christiane SchlechtHubertus Jarry
May 2, 2008·Toxicology·Hee-Kyung JeonJae-Chun Ryu
Jun 4, 2008·Pharmacogenomics·Christian P Strassburg
Aug 19, 2008·Toxicology and Applied Pharmacology·José-Manuel Molina-MolinaPatrick Balaguer
Oct 16, 2008·Current Drug Metabolism·M N JacobsB van der Burg
May 1, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Peter Josef HofmannJosef Köhrle
Feb 11, 2010·Analytical and Bioanalytical Chemistry·M Teresa DonatoAgustín Lahoz
Oct 1, 1997·Toxicology in Vitro : an International Journal Published in Association with BIBRA·G de SousaR Rahmani
Oct 14, 2010·Journal of Enzyme Inhibition and Medicinal Chemistry·Yuping LiuRenke Dai
May 13, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Elisabete SilvaAndreas Kortenkamp
Feb 4, 2012·Current Drug Metabolism·Pius FasinuBernd Rosenkranz
Jan 18, 2014·Reproduction : the Official Journal of the Society for the Study of Fertility·Andreas KortenkampSibylle Ermler
Jul 17, 2014·Toxicological Sciences : an Official Journal of the Society of Toxicology·Georges de SousaRoger Rahmani
Apr 5, 2015·Environmental Pollution·Chong-Jing GaoKurunthachalam Kannan

❮ Previous
Next ❯

Citations

Jun 19, 2016·Toxicology and Applied Pharmacology·S TengA R R Pery

❮ 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.