Human Erythrocytes Exposed to Phthalates and Their Metabolites Alter Antioxidant Enzyme Activity and Hemoglobin Oxidation.

Paulina Sicińska,Kinga Kik,Bożena Bukowska

doi:10.3390/ijms21124480

Paulina Sicińska, Kinga Kik + Show 1 more

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https://doi.org/10.3390/ijms21124480

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Abstract

Phthalates used as plasticizers have become a part of human life because of their important role in various industries. Human exposure to these compounds is unavoidable, and therefore their mechanisms of toxicity should be investigated. Due to their structure and function, human erythrocytes are increasingly used as a cell model for testing the in vitro toxicity of various xenobiotics. Therefore, the purpose of our study was to assess the effect of selected phthalates on methemoglobin (metHb), reactive oxygen species (ROS) including hydroxyl radical levels, as well as the activity of antioxidative enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), in human erythrocytes. Erythrocytes were incubated with di-n-butyl phthalate (DBP), butylbenzyl phthalate (BBP), and their metabolites, i.e., mono-n-butyl phthalate (MBP) and monobenzyl phthalate (MBzP), at concentrations ranging from 0.5 to 100 µg/mL for 6 or 24 h. This study shows that the analyzed phthalates disturbed the redox balance in human erythrocytes. DBP and BBP, at much lower concentrations than their metabolites, caused a statistically significant increase of metHb and ROS, including hydroxyl radical levels, and changed the activity of antioxidant enzymes. The studied phthalates disturbed the redox balance in human erythrocytes, which may contribute to the accelerated removal of these cells from the circulation.

Highlights

Nowadays, the list of substances that can have a serious impact on human health and the environment is systematically growing
DPB caused a statistically significant increase in the parameter studied starting from the concentration of 2.5 μg/mL, while butylbenzyl phthalate (BBP) produced this effect from the concentration of
A statistically significant increase in metHB level was observed in red blood cells (RBCs) treated with mono-n-butyl phthalate (MBP) and monobenzyl phthalate (MBzP) only starting from a concentration of 50 μg/mL (Table 1)

Summary

Introduction

The list of substances that can have a serious impact on human health and the environment is systematically growing. The European Chemicals Agency (ECHA) has identified these harmful chemicals as substances of very high concern (SVHC) This list includes phthalates (PAEs), which are the most commonly used plasticizers in the world. Phthalates do not form covalent bonds with the substances they are being added to and they may migrate and enter food, water, air, cosmetics, and various products of everyday use [5,6,7]. These compounds enter the human body mainly via the enteral pathway (food, water, drugs) at about 7–10 μg/kg of body weight (BW)/day and by inhalation (concentration in the air: BBP 0.058–3.97mg/m3 , DBP 1.5–270 ng/m3 ) or through dermal contact with cosmetics (DBP max 0.594 ppm and BBP max 186.770 ppm) [7,8,9,10].

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