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

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.

The The influence of high doses of α-tocopherol on the content of selected trace elements in the liver of developing chicken embryos in experimentally induced 2,3,7,8-tetrachlorodibenzo-p-dioxin intoxication

“…Hilscherova and others (Hilscherova et al, 2003) had found that dioxins cause oxidative DNA damage in chicken embryo livers by increasing the amounts of reactive oxygen species produced and depleting glutathione. In a study conducted by Gostomska-Pampuch and others (Gostomska-Pampuch et al, 2017), TCDD and α-tocopherol caused delayed liver development. In our study, the retarded growth of the liver may explain the statistically nonsignificant and small increase in the iron content in all experimental groups.…”

“…The authors would like to thank Prof. Ireneusz Całkosiński (1951Całkosiński ( -2017 for inspiration and helpful advice, as well as help with respect to organization and ensuring welfare of the animals.…”

“…Increased TCDD levels are found in the free-range system eggs due to the fact that hens are more exposed to TCDD in a free-range production system. In a chicken embryo, TCDD administered into the yolk may alter development of numerous organs, including the liver (De Vries, Kwakkel, & Kijlstra, 2006;Gostomska-Pampuch et al, 2017). In one study, Całkosiński (Całkosiński, 2008) exposed rats to TCDD and treated them for 3 weeks with high α-tocopherol doses (30 mg/(kg b.w.…”

Indirect study of the effect of α-tocopherol and acetylsalicylic acid on the mineral composition of bone tissue in the offspring of female rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin: long-term observations

“…3,13,15,16 Dioxins which connect with the AhR cause a migration of the receptor into the cell nucleus, which induces the expression of genes for cytochromes. [17][18][19] Furthermore, dioxins have an affinity for the estrogen receptor and owing to this they contribute to reproductive disorders and behavioral disorders associated with the occurrence of changes in the expression of receptors in the central nervous system structures. 17 The most signicant documented adverse effects of dioxins include: chloracne, changes in the level of thyroid hormones with impairment of the psychomotor abilities, fertility problems or infertility, increased concentration of alpha-and betaglobulins and delayed immune response, and carcinogenic and teratogenic effects in humans.…”

Modulating effect of selected pharmaceuticals on bone in female rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

“…3 The promising positive effects by tocopherol on structural and functional prevention of organs in the experimental intoxication by dioxins have prompted the authors to compare well known anti-inammatory and immunomodulating drugs on bone metabolism. [9][10][11][12][13] It was shown that administration of tocopherol or acetylsalicylic acid in mothers exposed to TCDD prevent decreases in calcium and magnesium concentrations in the calvaria of the offspring. 1 Moreover a protective effect of a low dose of a-tocopherol on Mg and Ca level in the bone of rat offspring aer intoxicating rat female rats with TCDD before insemination was evidenced.…”