Protective effects of levamisole, acetylsalicylic acid, and \u03b1-tocopherol against dioxin toxicity measured as the expression of AhR and COX-2 in a chicken embryo model

Kinga Gostomska-Pampuch,Ewa Łukaszewicz,Piotr Ziółkowski,Alicja Ostrowska,Ireneusz Całkosiński,Andrzej Gamian,Maciej Dobrzyński,Artur Kowalczyk,Piotr Kuropka

doi:10.1007/s00418-016-1528-2

Abstract

Polychlorinated dibenzo-p-dioxins and dibenzofurans (dioxins) are classed as persistent organic pollutants and have adverse effects on multiple functions within the body. Dioxins are known carcinogens, immunotoxins, and teratogens. Dioxins are transformed in vivo, and interactions between the products and the aryl hydrocarbon receptor (AhR) lead to the formation of proinflammatory and toxic metabolites. The aim of this study was to determine whether α-tocopherol (vitamin E), acetylsalicylic acid (ASA), and levamisole can decrease the amount of damage caused by dioxins. Fertile Hubbard Flex commercial line chicken eggs were injected with solutions containing 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or containing TCDD and the test compounds. The chicken embryos and organs were analyzed after 7 and 13 days. The levels at which AhR and cyclooxygenase-2 (COX-2) proteins (which are induced during inflammation) were expressed were evaluated by performing immunohistochemical analyses on embryos treated with TCDD alone or with TCDD and the test compounds. TCDD caused developmental disorders and increased AhR and COX-2 expression in the chicken embryo tissues. Vitamin E, levamisole, ASA, and ASA plus vitamin E inhibited AhR and COX-2 expression in embryos after 7 days and decreased AhR and COX-2 expression in embryos after 13 days. ASA, levamisole, and ASA plus vitamin E weakened the immune response and prevented multiple organ changes. Vitamin E was not fully protective against developmental changes in the embryos.

Highlights

Polychlorinated dibenzo-p-dioxins and dibenzofurans are hazardous chemicals that are classed as persistent organic pollutants
The control group (Group 1) embryos collected on day 7 showed aryl hydrocarbon receptor (AhR) expression, in the mesenchyme and dorsal epidermis
Dioxins affect the body in multiple ways, causing reproduction and development disorders, immunotoxicity, thymus involution, liver damage, and cancer

Summary

Introduction

Polychlorinated dibenzo-p-dioxins and dibenzofurans (dioxins) are hazardous chemicals that are classed as persistent organic pollutants. With half-lives of 7–8 years in humans. Dioxins are resistant to degradation in the environment, can be transported long distances in the air, and directly threaten environmental and human health (Całkosinski et al 2011; Wrbitzky et al 2001). Humans can be exposed to dioxins through skin contact (typically 2% of total exposure), inhaling air (typically 8% of total exposure), and ingesting contaminated water or food (typically 90% of total exposure) (Całkosinski et al 2011). The penetration of dioxins through the skin is facilitated by the lipid layer of the skin coming into direct contact with soot, ash, or contaminated clothing (Całkosinski et al 2005). Humans are primarily exposed to dioxins through ingesting food containing dioxins (Travis and Nixon 1991). In experiments using laboratory animals, dioxins have been found to accumulate in the skin and muscles (Zukiewicz-Sobczak et al 2012)

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