The skin surface of hydration determination, that is, the stratum corneum (SC), is an important tool for the evaluation of its barrier capacity, as well as the proper functioning of cutaneous processes such as cellular metabolism, hydrolytic enzymatic processes needed for normal desquamation, and maturation of the SC. In addition, an adequate amount of water is important for a healthy, smooth, and flexible skin appearance. 1,2 This barrier characteristic of SC is related to its unique physicochemical composition and structure of several layers of flattened and keratinized cells (corneocytes) suspended in extracellular lipid matrix. The corneocytes are anucleated cells filled with keratin filaments attached to a cornified peripheral envelope, composed of protein cross-links. In addition, on the outer
Bisphenol A (BPA) is a well-known endocrine disruptor with several effects on reproduction, development, and cancer incidence, and it is highly used in the plastic industry. Bisphenol S (BPS) was proposed as an alternative to BPA since it has a similar structure and can be used to manufacture the same products. Some reports show that BPA interferes with thyroid function, but little is known about the involvement of BPS in thyroid function or how these molecules could possibly modulate at the same time the principal genes involved in thyroid physiology. Thus, the aims of this work were to evaluate in silico the possible interactions of BPA and BPS with the thyroid transcription factors Pax 8 and TTF1 and to study the actions in vivo of these compounds in zebrafish thyroid gene expression. Adult zebrafish treated with BPA or BPS showed that sodium iodide symporter, thyroglobulin, and thyroperoxidase genes were negatively or positively regulated, depending on the dose of the exposure. Human Pax 8 alignment with zebrafish Pax 8 and Rattus norvegicus TTF1 alignment with zebrafish TTF1 displayed highly conserved regions in the DNA binding sites. Molecular docking revealed the in silico interactions between the protein targets Pax 8 and TTF1 with BPA and BPS. Importance of some amino acids residues is highlighted and ratified by literature. There were no differences between the mean energy values for BPA docking in Pax 8 or TTF1. However, BPS energy values were lower in TTF1 docking compared to Pax 8 values. The number of amino acids on the protein interface was important for Pax 8 but not for TTF1. The main BPA interactions with proteins occurred through Van der Waals forces and pi-alkyl and alkyl interactions, while BPS interactions mainly occurred through carbon hydrogen bonds and conventional hydrogen bonds in addition to Van der Waals forces and pi-alkyl interactions. These data point to a possible interaction of BPA and BPS with Pax 8 and TTF1.
Zebrafish has been established as a reliable biological model with important insertion in academy (morphologic, biochemical, and pathophysiological studies) and pharmaceutical industry (toxicology and drug development) due to its molecular complexity and similar systems biology that recapitulate those from other organisms. Considering the toxicological aspects, many efforts using zebrafish models are being done in order to elucidate the effects of endocrine disruptors, and some of them are focused on tributyltin (TBT) and its mechanism of action. TBT is an antifouling agent applied in ship’s hull that is constantly released into the water and absorbed by marine organisms, leading to bioaccumulation and biomagnification effects. Thus, several findings of malformations and changes in the normal biochemical and physiologic aspects of these marine animals have been related to TBT contamination. In the present review, we have compiled the most significant studies related to TBT effects in zebrafish, also taking into consideration the effects found in other study models.
Background: Ang II (Ang II) regulates blood volume and stimulates erythropoiesis through AT1 (ATR1) and AT2 (ATR2) receptors, being found in multiple tissues, including erythrocytes. Sickle cell disease (SCD) patients presents altered Ang II (Ang II) levels.Hypothesis: Hemoglobin S polymerization, erythrocyte adhesion, deformability and eryptosis are important features of mature erythrocyte, therefore, our hypothesis is Ang II affect these parameters and, if does, which would be the in uence of AT1R and AT2R in these effects.Methods: A Polymerization Assay (PA), static adhesion, deformability and annexin V binding were performed in SCD erythrocytes samples adding Ang II, ATR1 antagonist (losartan or eprosartan), and ATR2 antagonist (PD123319).Results: Through the PA test, we observed a dose-dependent polymerization inhibition effect when comparing Ang II to control. Losartan did not affect nor the level nor the rate of Ang II inhibition, while PD123319 showed an increased level of protection against polymerization and eprosartan brought levels back to control. Ang II does not change static adhesion but was able to reduce eryptosis in the presence of PD123319. Also, ATR1 shows a positive effect increasing deformability. Conclusion: our data shows that ATR1 is important for maintenance of erythrocyte physiological function in SCD and for prolonging its life.
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