The possible thyroid disruptive effect of di-(2-ethyl hexyl) phthalate and the potential protective role of selenium and curcumin nanoparticles: a toxicological and histological study

Abstract

Di-(2-ethylhexyl) phthalate (DEHP) is one of the ubiquitous pollutants worldwide. This study aimed to clarify the potential thyroid disrupting effect of DEHP and explore the probable ameliorative effects of selenium nanoparticles (Se-NPs) and curcumin nanoparticles (CUR-NPs). Forty-two male albino rats were divided into seven groups (n = 6): Group I (negative control); group (II) orally received DEHP (500 mg/kg BW, dissolved in corn oil); Group (III) orally received Se-NPs (.2 mg/kg BW) in combination with DEHP; Group (IV) orally received CUR-NPs (15 mg/kg BW) alongside with DEHP; Group V (corn oil); Group VI (Se-NPs) and Group VII (CUR-NPs). The duration of the experiment was 30 days. DEHP administration significantly decreased serum free T4 and significantly increased serum free T3 as compared to control group, whereas thyroid-stimulating hormone showed no significant change. DEHP disrupted redox status leading to accumulation of malondialdehyde and depletion of reduced glutathione. Histologically, the effect of DEHP on thyroid follicles was confirmed by light and electron microscopic examination and morphometric analysis. Se-NPs slightly improved thyroid parameters as well as redox status. CUR-NPS reinstated the values of all studied thyroid parameters to nearly control levels. This research provides Se-NPs and CUR-NPs as novel protective agents against DEHP-thyroid disrupting effects.

Insights into the Endocrine Disrupting Activity of Emerging Non-Phthalate Alternate Plasticizers against Thyroid Hormone Receptor: A Structural Perspective

“…Nevertheless, the early exposure of phthalates may have a potential impact on organogenesis, including neurodevelopment in children, as the thyroid hormones are critically essential for the nervous system during the fetal and early neonatal life [ 52 ]. DEHP has also been shown to induce thyroid toxicity and perturb the homeostasis of thyroid hormones in laboratory animals [ 47 , 53 ]. In rats, DEHP caused interference in the hypothalamic-pituitary-axis and lowered the concentrations of free T3, total T3, free T4, and total T4 along with protein and mRNA levels of thyroid stimulating hormone [ 47 ].…”

“…In rats, DEHP caused interference in the hypothalamic-pituitary-axis and lowered the concentrations of free T3, total T3, free T4, and total T4 along with protein and mRNA levels of thyroid stimulating hormone [ 47 ]. In another study in rats [ 53 ], along with lowering of T4 and increasing of T3, disruption of the redox status, accumulation of malondialdehyde, and depletion of reduced glutathione was found together with histological changes in thyroid follicles [ 53 ]. Similar effects have been reported in several other studies [ 40 , 54 ].…”

Selenium, Iodine and Iron–Essential Trace Elements for Thyroid Hormone Synthesis and Metabolism

“…This variability is one reason for the divergence in clinical (pilot) studies which mainly are underpowered, short and lack clear information on basal Se status and the detailed speciation of the Se content of the preparations used [ 18 , 103 ]. Recently, novel forms of Se supplements entered the OTC, and the online and internet market of Se compounds and were appraised as next-generation Se supplements less toxic than previous traditional inorganic forms (selenite or selenate) because they apparently bypass classical cellular uptake mechanisms for inorganic anions or the amino acids Sec and SeMet [ 104 , 105 , 106 , 107 , 108 ]. These cellular ‘mini-taxis’, assumed to deliver the essential trace element bound to various bioactive carrier and coating molecules, are rapidly absorbed by cell membranes and may prevent interference with the cellular redox control system rapidly metabolizing selenite and selenate.…”

Intrauterine exposure to di(2-ethylhexyl) phthalate (DEHP) disrupts the function of the hypothalamus-pituitary-thyroid axis of the F1 rats during adult life

“…Although the female rats presented decreased expression of genes/proteins involved in thyroid hormone production, T3 levels were increased in the lowest treatment dose. Previous data indicated increased T3 serum levels and decreased T4 levels in animals exposed to DEHP (300 mg of DEHP/kg/day) (40,53).…”