N-acetylcysteine potentiates diclofenac toxicity in Saccharomyces cerevisiae: stronger potentiation in ABC transporter mutant strains

Drug and Chemical Toxicology
Houssein Al-AttracheZiad Abdel-Razzak

Abstract

Diclofenac (DCF) adverse reactions involve diverse mechanisms in different models. We recently demonstrated that DCF-induced toxicity in HepaRG decreases as they express DCF-metabolizing enzymes. DCF metabolism promotes toxicity in Saccharomyces cerevisiae expressing heterologous cytochromes-P450. N-Acetylcysteine (NAC) is used to treat diverse medical conditions due to its multiple properties (antioxidant, metal chelator, thiol-disulfide disruption). The latter property accounts for its mucolytic effects and broadens its potential molecular targets to signal transduction proteins, ABC transporters and others. Interaction of NAC with DCF effects depends on the experimental model. This study aims to investigate NAC/DCF interaction and the involvement of ABC transporters in wild type and mutant Saccharomyces cerevisiae. DCF inhibited yeast growth in a dose- and time-dependent manner and the cells started adapting to DCF 24-h post-treatment. NAC potentiated DCF-induced toxicity if added prior or parallel to DCF. Pretreatment with NAC increased its potentiation effect and compromised cells adaption to DCF. Post-treatment with NAC potentiated DCF toxicity without compromising adaptation. Moreover, mutant strains in ABC transporters ...Continue Reading

References

Nov 1, 1986·Gut·E G BreenF M Stevens
Sep 1, 1995·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·A T BanksJ G Harter
Dec 28, 1999·Annual Review of Cell and Developmental Biology·J Chant
May 18, 2001·Biochemical Society Transactions·J T HancockS J Neill
Mar 1, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yasuhiro MasubuchiToshiharu Horie
May 25, 2002·The Journal of Biological Chemistry·You Cheng XuLance S Terada
Mar 5, 2003·Cellular and Molecular Life Sciences : CMLS·M ZafarullahM Ahmad
Oct 25, 2003·Toxicology and Applied Pharmacology·Urs A Boelsterli
Nov 12, 2003·Biochemical Pharmacology·M José Gómez-LechónRamiro Jover
Aug 12, 2004·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·A G WangM P Waalkes
Aug 30, 2005·Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology·Esther Edlundh-RoseJoakim Lundeberg
Apr 3, 2007·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Shai EfratiAhuva Golik
May 23, 2007·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Norihito WatanabeShohei Matsuzaki
Apr 16, 2009·The Journal of Biological Chemistry·Maika DeffieuNadine Camougrand
Dec 23, 2009·Microbial Pathogenesis·Zahra Rashki GhalehnooAngel Dominguez
Jul 6, 2010·TheScientificWorldJournal·Tiziana ParasassiFulvio Ursini
Nov 30, 2010·Toxicology Letters·Jolanda S van LeeuwenNico P E Vermeulen
Mar 25, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Lisa FredrikssonBob van de Water
Feb 6, 2010·World Journal of Gastrointestinal Pharmacology and Therapeutics·Laura Ramudo, Manuel A Manso
Apr 27, 2013·Biochimica Et Biophysica Acta·Yuval SamuniMichael Berk
Dec 4, 2013·Cellular & Molecular Biology Letters·Agata Piecuch, Ewa Obłąk
Apr 23, 2014·Toxicological Sciences : an Official Journal of the Society of Toxicology·Lisa FredrikssonBob van de Water
Jan 2, 2015·Frontiers in Bioscience (Landmark Edition)·Yongqing HouGuoyao Wu
May 9, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ashley R MaiuriRobert A Roth

❮ Previous
Next ❯

Citations

Jan 9, 2021·FEMS Yeast Research·Sheila Tiemi NagamatsuMarcelo Falsarella Carazzolle
Mar 20, 2020·Interdisciplinary Toxicology·Dina MuhieddineZiad Abdel-Razzak

❮ 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.