N-terminal globin adducts as biomarkers for formation of butadiene derived epoxides

Boysen, Gunnar; Georgieva, Nadia I.; Upton, Patricia B.; Walker, Vernon E.; Swenberg, James A.

doi:10.1016/j.cbi.2006.10.005

Cited by 36 publications

(42 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(3a) and (3b)) from the published data for BD-exposed mice and rats, data on Hb adduct levels of EB, DEB and EBdiol from Swenberg and co-workers (Bordeerat, 2011;Boysen et al, 2007;Georgieva et al, 2010) were used. To determine the EB-Val and EBdiol-Val, the alkylated N-terminal valines (Boysen et al, 2007;Osterman-Golkar et al, 1991) were selectively detached as fluorinated derivatives by using a modified Edman degradation method and then analyzing by GC-MS (cf. Törnqvist et al, 1986).…”

Section: Methodsmentioning

confidence: 99%

“…A method based on the trypsin digestion of globin was developed to analyze the ring-closed DEB-Val (Boysen et al, 2005;Fred et al, 2004b). The resulting DEBmodified N-terminal α-heptapeptide was enriched by immunoaffinity chromatography prior to LC-MS/MS analysis (Boysen et al, 2005(Boysen et al, , 2007.…”

Section: Methodsmentioning

confidence: 99%

“…In this procedure, only the adducts to the N-terminal valine in the α-chain were measured (Boysen et al, 2005(Boysen et al, , 2007. However, the reaction rate constant used to calculate the AUC in Eq.…”

Section: Methodsmentioning

confidence: 99%

“…In blood taken from BD-exposed mice and rats, hemoglobin (Hb) adducts from the three epoxides have been measured as N-(2-hydroxy-3-butenyl)-valine (EB-Val), N,N-(2,3-dihydroxy-1,4-butadiyl)-valine (DEB-Val) and N-(2,3,4-trihydroxybutyl)-valine (EBdiol-Val) (cf. Scheme 1) (Boysen et al, 2005(Boysen et al, , 2007Georgieva et al, 2010;Osterman-Golkar et al, 1998). Data on Hb adduct levels from BD monoepoxides is available from a relatively large number of Toxicology and Applied Pharmacology xxx (2014) xxx-xxx ⁎ Corresponding author.…”

mentioning

confidence: 99%

See 3 more Smart Citations

In vivo doses of butadiene epoxides as estimated from in vitro enzyme kinetics by using cob(I)alamin and measured hemoglobin adducts: An inter-species extrapolation approach

Motwani

Törnqvist

2014

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

In vivo doses of butadiene epoxides as estimated from in vitro enzyme kinetics by using cob(I)alamin and measured hemoglobin adducts: An inter-species extrapolation approach

Motwani

Törnqvist

2014

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

“…Covalent adducts formed with abundant and easily accessible blood proteins, like Hb and human serum albumin, can be good biomarkers of drug bioactivation to reactive metabolites and drug proteinmodification and are frequently used to study the ability of drug metabolites to undergo protein haptenation. In particular, adducts formed by N-terminal valine residues of Hb have been extensively applied for that purpose (Boysen et al, 2007;Chevolleau et al, 2007). The widespread use of these species can be explained on the basis of the high accessibility of xenobiotics to N-terminal valine residues in Hb and the fact that a large fraction of these residues are unionized, and therefore nucleophilic, at blood pH (Moll and Elfarra, 1999;Törnqvist et al, 2002), which explains why they are especially prone to react with electrophilic metabolites forming covalent adducts.…”

Section: Discussionmentioning

confidence: 99%

Evidence for nevirapine bioactivation in man: Searching for the first step in the mechanism of nevirapine toxicity

Caixas¹,

Antunes²,

Marinho³

et al. 2012

Toxicology

View full text Add to dashboard Cite

a b s t r a c tDespite its efficacy, including in the prevention of vertical transmission, the antiretroviral nevirapine is associated with severe idiosyncratic hepatotoxicity and skin rash. The mechanisms underlying nevirapine toxicity are not fully understood, but drug bioactivation to reactive metabolites capable of forming stable protein adducts is thought to be involved. This hypothesis is based on the paradigm that drug reactive metabolites have the potential to bind to self-proteins, which results in drug-modified proteins being perceived as foreign by the immune system. The aim of the present work was to identify hemoglobin adducts in HIV patients as biomarkers of nevirapine haptenation upon bioactivation. The ultimate goal is to develop diagnostic methods for predicting the onset of nevirapine-induced toxic reactions.All included subjects were adults on nevirapine-containing antiretroviral therapy for at least 1 month. The protocol received prior approval from the Hospital Ethics Committees and patients gave their written informed consent. Nevirapine-derived adducts with the N-terminal valine of hemoglobin were analyzed by an established liquid chromatography-electrospray ionization-tandem mass spectrometry method and characterized on the basis of retention time and mass spectrometric fragmentation pattern by comparison with adduct standards prepared synthetically. The nevirapine adducts were detected in 12/13 patient samples, and quantified in 11/12 samples (2.58 ± 0.8 fmol/g of hemoglobin).This work represents the first evidence of nevirapine-protein adduct formation in man and confirms the ability of nevirapine to modify self-proteins, thus providing clues to the molecular mechanisms underlying nevirapine toxicity. Moreover, the possibility of assessing nevirapine-protein adduct levels has the potential to become useful for predicting the onset of nevirapine-induced adverse reactions.© 2012 Published by Elsevier Ireland Ltd.Abbreviations: cART, combined antiretroviral therapy; CID, collision-induced dissociation; GSH, glutathione; Hb, hemoglobin; HIV, human immunodeficiency virus; HLA, human leukocyte antigen; 12-OH-NVP, 12-hydroxy-nevirapine; LC-ESI-MS/MS, liquid chromatography-electrospray ionization-tandem mass spectrometry; MHC, major histocompatibility complex; NNRTI, non-nucleoside reverse transcriptase inhibitor; NVP, nevirapine.* Corresponding author.

show abstract

Epoxy Compounds—Olefin Oxides (Ethylene Oxide, Propylene Oxide, and Miscellaneous Oxides)

Klapacz

Doskey

2023

Patty's Toxicology

View full text Add to dashboard Cite

This chapter discusses the chemistry, uses, health information, and industrial hygiene handling procedures of epoxides, that is, substances containing strained, three‐membered rings with two adjacent carbons and one oxygen atom. This functionality underlies epoxides' high reactivity, physicochemical properties, and toxicity. The majority of the content is dedicated to ethylene oxide and propylene oxide, but other epoxides are also of industrial interest and are described here; their databases have evolved over the last couple of decades and this new understanding is highlighted here. These are 1,2‐butylene oxide, 2,3‐epoxybutane, butadiene diepoxide, vinylcyclohexene monoxide, vinylcyclohexene dioxide, and styrene oxide.

show abstract

N-terminal globin adducts as biomarkers for formation of butadiene derived epoxides

Cited by 36 publications

References 35 publications

In vivo doses of butadiene epoxides as estimated from in vitro enzyme kinetics by using cob(I)alamin and measured hemoglobin adducts: An inter-species extrapolation approach

In vivo doses of butadiene epoxides as estimated from in vitro enzyme kinetics by using cob(I)alamin and measured hemoglobin adducts: An inter-species extrapolation approach

Evidence for nevirapine bioactivation in man: Searching for the first step in the mechanism of nevirapine toxicity

Epoxy Compounds—Olefin Oxides (Ethylene Oxide, Propylene Oxide, and Miscellaneous Oxides)

Contact Info

Product

Resources

About