Factors Influencing the Formation of Chemical-Hemoglobin Adducts.

Yuko Shimamura,Akina Okuda,Kenya Ichikawa,Shuichi Masuda,Sohei Ito,Hiroshi Honda,Ryo Inagaki

doi:10.3390/toxics10010002

Abstract

Hemoglobin (Hb) adducts have been used as biomarkers for the internal exposure to chemicals. Simultaneous exposure to chemicals that bond with the N-terminal valine of Hb to form adducts, such as glycidol, acrylamide, and glucose, may affect the formation of the individual Hb adducts. In this study, various factors influencing the formation of chemical–Hb adducts were analyzed using in vitro and in vivo systems. In the in vitro assays, the formation of glycidol– and acrylamide–Hb adducts was altered in the presence of glucose, serum albumin, and other chemicals. In contrast, in the in vivo experiments, glycidol– and acrylamide–Hb adduct formation was unchanged in mice exposed to glycidol and acrylamide. The interaction between glycidol and acrylamide with residues other than the N-terminal valine of Hb was analyzed using the protein thermal shift assay. Glycidol and acrylamide also interacted with amino acid residues other than the N-terminal valine of Hb. The presence of other blood components, such as amino acids, may affect the formation of chemical–Hb adducts. Further research is expected to elucidate the remaining unknown factors that affect the formation of chemical–Hb adducts.

Highlights

Academic Editor: Hitesh V.In recent years, the presence of glycidol fatty acid esters (GEs) has been detected in foods such as cooking oil
The Hb concentration glycidol concentration of 250 mM or higher, it was considered that the amount of glycidol–Hb adduct decreased owing to the change in the structure of Hb induced by the toxicity of the excessive concentration of glycidol
At a glycidol concentration of 250 mM or higher, it was considered that the amount of glycidol–Hb adduct decreased owing to the change in the structure of Hb induced by the toxicity of the excessive concentration of glycidol

Summary

Introduction

Academic Editor: Hitesh V.In recent years, the presence of glycidol fatty acid esters (GEs) has been detected in foods such as cooking oil. As glycidol is known as a mutagen and rodent carcinogen [2], the presence of GEs in foods has become a major societal problem. Given the concerns about the effects of mutations and carcinogens, such as glycidol, on human health, it is important to understand the level of dietary exposure to these chemical substances in humans and the early chemical effects in vivo. Screening methods using substance exposure indicators (biomarkers) have been developed. Hemoglobin (Hb) adducts, produced when a chemical substance binds hemoglobin, the main component of erythrocytes, have attracted attention [3]. The formation of a hemoglobin adduct of glycidol occurs when glycidol binds to the N-terminal valine of the Hb structure [4,5]. N-(2,3-Dihydroxypropyl)valine is a hemoglobin adduct of glycidol and is used as a marker for internal exposure to glycidol [3,6–8]

Methods

Discussion

Conclusion