Tributyltin and Zebrafish: Swimming in Dangerous Water

Abstract

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.

Zebrafish Larvae as a Behavioral Model in Neuropharmacology

“…For instance, arsenic showed increased locomotor activity [98] and tributyltin significantly reduced the locomotor activity [103] in zebrafish larvae. These effects were similar to that described in the rodent models where arsenic is shown to cause an increase in locomotor activity [98] and tributyltin is shown to cause a dose-dependent decrease in spontaneous motor activity [117]. Thus, the light-dark locomotion test in zebrafish larvae has been successfully employed for the study of neurobehavioral alterations caused by various environmental toxicants.…”

Transcriptomic effects of tributyltin (TBT) in zebrafish eleutheroembryos. A functional benchmark dose analysis

“…On the other hand, our results also showed TBT effects in genes implicated in lipid metabolism and fatty acid biosynthesis pathways, which is consistent with an observed lipidic disruption previously reported in similar experimental setups (den Broeder et al, 2017). However, lipid dysregulation took place only at relatively high TBT concentrations, and it was limited to the transcriptomic level (Berto-Júnior et al, 2018;Grün, 2014;Ouadah-Boussouf and Babin, 2016;Tingaud-Sequeira et al, 2011). The induction of yolk-sac malabsorption syndrome or energy consumption dysregulation by TBT has not been found at this stage of development (5 dpf) (Liang et al, 2017;Martínez et al, 2019a), and J o u r n a l P r e -p r o o f obesogenic effects only appear at later larval stages (15 dpf, (den Broeder et al, 2017)).…”

Environmental Health and Toxicology: Immunomodulation Promoted by Endocrine-Disrupting Chemical Tributyltin

“…Interestingly, TBT has also been described as an antagonist of human ERs by inhibiting the transcriptional activation of the ER-dependent reporter gene and the interaction between the ligand-binding domain of the β isoform (ERβ LBD) and the steroid receptor coactivator-1 (SRC1) [ 58 , 59 ]. Additionally, TBT acts as an inhibitor of aromatase, the enzyme accountable for the conversion of testosterone to estrogen, as well as the estrogen receptor in zebrafish, thereby reducing the effects of ethinylestradiol [ 60 ]. Additionally, numerous studies have revealed that TBT disrupts estrogen signaling, affecting various tissues, as shown in Figure 1 [ 28 , 30 , 33 , 61 , 62 , 63 , 64 , 65 ].…”