Differential cytotoxicity of Ifosfamide and its metabolites in renal epithelial cell cultures

Toxicology in Vitro : an International Journal Published in Association with BIBRA
C L BroadheadN L Simmons

Abstract

Ifosfamide (IF) chemotherapy is dependent on bioactivation by cytochrome P-450 and may be limited by concurrent nephrotoxicity. An in vitro approach utilizing the renal cell lines G401, MDCK Strains I and II, LLCPK1 and OK has been adopted to study nephrotoxic actions of IF and its known metabolites, 4-hydroperoxy-ifosfamide (4-OOH-IF, 4-OH-IF in solution), chloroacetaldehyde (CAA), isofosphoramide mustard (IF-mus) and acrolein using an MTT assay. IF is virtually non-toxic to the panel of renal cell lines used; prolonged incubation with ifosfamide led to a progressive reduction in cell MTT activity only in MDCKI (days 3, 4). 4-hydroxylation of IF was directly measured in MDCK microsomes; MDCKI microsomes gave an activity of 0.045nmol/min/mg, while in the MDCKII microsome preparation only 0.004nmol/min/mg was detected. The limited toxicity to IF observed in MDCKI may be explained in part by the ability of cell cytosol to activate IF by 4-hydroxylation. In contrast to IF, its metabolites applied extracellularly were toxic to the panel of renal cell lines used. This cytotoxicity varied within and between cell lines. In LLCPK1 cells after 48hr of exposure to IF metabolites, the toxicity as measured as a percentage of control MTT ac...Continue Reading

References

Jul 28, 1978·Biochemical and Biophysical Research Communications·S R GoldringS M Krane
Nov 1, 1992·Renal Physiology and Biochemistry·M MohrmannM Brandis
Jan 1, 1990·Methods in Enzymology·N L Simmons
Nov 22, 1986·Lancet·M P GorenF E Pell
Jan 1, 1988·Cancer Investigation·N BrockH Sindermann
Aug 20, 1987·Biochimica Et Biophysica Acta·K MalströmH Murer
Jan 1, 1985·Cancer Chemotherapy and Pharmacology·C R PinkertonJ Pritchard
Apr 1, 1994·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·M MohrmannM Brandis
Aug 1, 1994·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·M MohrmannM Brandis
Nov 1, 1994·Toxicology and Applied Pharmacology·M J Zamlauski-TuckerJ E Springate
Aug 30, 1994·Biochemical Pharmacology·C Sood, P J O'Brien
Jan 1, 1993·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·R SkinnerA W Craft
Apr 22, 1993·Biochemical Pharmacology·G F Weber, D J Waxman
Aug 31, 1996·Lancet·R SkinnerA W Craft
Jan 1, 1996·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·A E VickersJ Guertler
Aug 1, 1994·Toxicology in Vitro : an International Journal Published in Association with BIBRA·M BlackmoreT J Gray
Mar 1, 1993·Toxicology in Vitro : an International Journal Published in Association with BIBRA·J A Charlton, N L Simmons

❮ Previous
Next ❯

Citations

Oct 31, 2006·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·James Springate, Mary Taub
Jul 10, 2003·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Emad L ZakiMary Taub
Dec 18, 2013·Seminars in Oncology·Roderick SkinnerPaul C Nathan
Apr 5, 2011·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Clelia RamelloEric Leclerc
Dec 15, 2004·Archiv der Pharmazie·Angela M OttoBernhard Wolf
May 8, 2010·Expert Opinion on Drug Metabolism & Toxicology·Bérénice GiraudAngelo Paci
May 7, 2014·PloS One·Marta TorrenteFrançois Verrey
Aug 23, 2017·Toxicology Mechanisms and Methods·Jayme P CoyleRaymond D Harbison
Dec 21, 2018·JCI Insight·Elijah J WeberEdward J Kelly

❮ 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.