Tributyltin-induced visceral adiposity is associated with impaired redox balance in white adipose tissue of male rats.

Tributyltin (TBT) is an organotin compound that has several adverse health effects, including the development of obesity. Although obesity is strongly associated with adipose redox imbalance, there is a lack of information on whether TBT promotes a pro-oxidative environment in WAT. Thus, adult male Wistar rats were randomly exposed to either vehicle (ethanol 0.4%) or TBT (1000 ng/kg) for 30 days. Body and fat pad masses, visceral fat morphology, lipid peroxidation, protein carbonylation, redox status markers, and catalase activity were evaluated. TBT promoted increased adiposity and visceral fat, with hypertrophic adipocytes, but did not alter body mass and subcutaneous fat. ROS production and lipid peroxidation were elevated in TBT group, as well as catalase protein expression and activity, although protein oxidation and glutathione peroxidase protein expression remained unchanged. In conclusion, this is the first study to demonstrate that subacute TBT administration leads to visceral adipose redox imbalance, with increased oxidative stress. This enlights the understanding of the metabolic toxic outcomes of continuous exposure to TBT in mammals.

Effect of tributyltin exposure on the embryonic development and behavior of a molluscan model species, Lymnaea stagnalis.

The presence of the organotin compound tributyltin (TBT) in aquatic ecosystems has been a serious environmental problem for decades. Although a number of studies described the negative impact of TBT on mollusks at different levels, investigations connected to its potential effects during embryogenesis have been neglected. For a better understanding of the impact of TBT on mollusks, in the present study, embryos of previously TBT-treated or not treated specimens of the great pond snail (Lymnaea stagnalis) were exposed to 100 ng L-1 TBT from egg-laying (single-cell stage) until hatching. According to our results, TBT significantly delayed hatching and caused shell malformation. TBT transiently decreased the locomotion (gliding) and also reduced the feeding activity, demonstrating for the first time that this compound can alter the behavioral patterns of molluscan embryos. The heart rate was also significantly reduced, providing further support that cardiac activity is an excellent indicator of metal pollution in molluscan species. At the histochemical level, tin was demonstrated for the first time in TBT-treated hatchlings with intensive reaction in the central nervous system, kidney, and hepatopancreas. Overall, the most notable effects were observed in treated embryos derived from TBT treated snails. Our findings indicate that TBT has detrimental effects on the development and physiological functions of Lymnaea embryos even at a sub-lethal concentration, potentially influencing their survival and fitness. Highlighting our observations, we have demonstrated previously unknown physiological changes (altered heart rate, locomotion, and feeding activity) caused by TBT, as well as visualized tin at the histochemical level in a molluscan species for the first time following TBT exposure. Further studies are in progress to reveal the cellular and molecular mechanisms underlying the physiological and behavioral changes described in the present study.

Subacute exposure to a mixture of tributyltin plus mercury impairs reproductive axis function, exacerbating premature ovarian insufficiency features and reducing fertility in female rats.

Tributyltin (TBT) and mercury (Hg) are endocrine-disrupting chemicals that individually cause reproductive complications. However, the reproductive consequences of exposure to a mixture of TBT plus Hg are not well known. We hypothesized that exposure to a mixture of TBT plus Hg would alter hypothalamic-pituitary-gonadal (HPG) axis function. Female rats were exposed to this mixture daily for 15 days, after which chemical accumulation in the tissues, morphology, hormone levels, inflammation, fibrosis, and protein expression in the reproductive organs were assessed. Increases in tin (Sn) and Hg levels were detected in the serum, HPG axis, and uterus of TBT-Hg rats. TBT-Hg rats exhibited irregular estrous cycles. TBT-Hg rats showed an increase in gonadotropin-releasing hormone (GnRH) protein expression and follicle-stimulating hormone (FSH) levels and a reduction in luteinizing hormone (LH) levels. Reduced ovarian reserve, antral follicles, corpora lutea (CL) number, and estrogen levels and increased atretic and cystic follicles were found, suggesting that TBT-Hg exposure exacerbated premature ovarian insufficiency (POI) features. Furthermore, TBT-Hg rats exhibited increased ovarian mast cell numbers, expression of the inflammatory markers IL-6 and collagen deposition. Apoptosis and reduced gland number were observed in the uteri of TBT-Hg rats. A reduction in the number of pups/litter for 90 days was found in TBT-Hg rats, suggesting impaired fertility. Strong negative correlations were found between serum and ovarian Sn levels and ovarian Hg levels and ovarian reserve and CL number. Collectively, these data suggest that TBT plus Hg exposure leads to abnormalities in the HPG axis, exacerbating POI features and reducing fertility in female rats.

Development of methodology for the visual identification of Tributyltin (TBT) in antifouling paint matrices.

Organotin compounds (OTC), mainly tributyltin (TBT), have been used since the 1970s as biocides in the composition of antifouling paints. Due to its physical-chemical characteristics, TBT has high toxicity to the marine environment affecting non-target organisms. The present study aims to develop a method of direct visual identification of TBT in antifouling paints using the cyclopalladate complex, 4- (2-thiazolylazo) resorcinol (TAR-Pd), synthesized in our laboratory. Tests were performed in blank and in the paint matrix with the following OTC: TBT-O; TBT-Cl; TPT-Cl; DBT-Cl (tributyltin oxide, tributyltin chloride, triphenyltin chloride, dibutyltin chloride), in addition to the SnCl4 and SnCl2 compounds (tin IV chloride and tin II chloride), all at a concentration of approximately 20 g/ kg of dry paint). The test was performed by applying paint samples to test bodies and scraping a few tens of milligrams of the dry paint film. The scraped paint samples were submitted to the test, showing a different staining reaction for the TBT-Cl and SnCl4 samples concerning blank and other samples (TBT-O, TPT, DBT-Cl, and SnCl2). Solution tests were performed to characterize reaction products by spectroscopy in the visible band. The method developed has potential for application in real samples, being selective for TBT-Cl and SnCl4 in an acid medium, obtaining a limit of detection, in the range of 1-10 mg/kg dry paint.

Subacute tributyltin exposure alters the development and morphology of mammary glands in association with CYP19A1 expression in female rats.

Tributyltin (TBT) is an endocrine-disrupting chemical (EDC) related to reproductive dysfunctions. However, few studies have investigated the effects of TBT exposure on mammary gland development. Thus, we assessed whether subacute TBT exposure causes irregularities in mammary gland development. We administered TBT (100 and 1,000 ng/kg/day for 30 days) to female rats from postnatal day (PND) 25 to PND 55, and mammary gland development, morphology, inflammation, collagen deposition, and protein expression were evaluated. Abnormal mammary gland development was observed in both TBT groups. Specifically, TBT exposure reduced the number of terminal end buds (TEBs), type 1 (AB1) alveolar buds, and type 2 (AB2) alveolar buds. An increase in the lobule and differentiation (DF) 2 score was found in the mammary glands of TBT rats. TBT exposure increased mammary gland blood vessels, mast cell numbers, and collagen deposition. Additionally, both TBT rats exhibited intraductal hyperplasia and TEB-like structures. An increase in estrogen receptor alpha (ERα), progesterone receptor (PR), and cytochrome P450 family 19 subfamily A member 1 (CYP19A1) - positive cells was observed in the mammary glands of TBT rats. A strong negative correlation was observed between CYP19A1- positive cells and TEB number. In addition, CYP19A1 - positive cells were positively correlated with mammary gland TEB-like structure, ductal hyperplasia, inflammation, and collagen deposition. Thus, these data suggest that TBT exposure impairs mammary gland development through the modulation of CYP19A1 signaling pathways in female rats.

Bioaccumulation of organotin compounds in the marbled electric ray (Torpedo marmorata) in the northern Adriatic Sea.

Organotin compounds (OTC), tri-, di- and monobutyl tin, were determined in the tissues of marbled electric ray (Torpedo marmorata) in the Adriatic Sea. Marbled electric ray specimens were provided by local fishermen from three localities in the northern Adriatic: area close to the shipyard in Seca, the natural protected area Strunjan Nature Reserve and along the west Istrian coast. To assess the concentration of OTC in the environment, sediment samples were also analysed. After an adequate extraction of OTC from both matrices, their concentrations were determined by GC-ICP-MS. The results indicate that the accumulation of TBT (tributyltin) and DBT (dibutyltin) in the marbled electric ray is related to the possible pollution sources, since their total concentrations were significantly higher (p < 0.001) in the area close to the shipyard (up to 69 µg Sn kg-1, w.w.) in comparison to the other two areas less affected by direct pollution (up to 7 µg Sn kg-1, w.w.). TBT concentrations ranged from 2 to 42 µg Sn kg-1, w.w., DBT concentrations were in the range from 2 to 22 µg Sn kg-1, w.w., and MBT concentrations were mostly below the detection limit with the highest up to 4 µg Sn kg-1, w.w. The proportion of the three determined congener concentrations in sediment samples indicate a temporally older pollution with these compounds, with prevailing DBT and MBT concentrations up to 30 µg Sn kg-1, w.w., and much lower TBT concentrations up to 7 µg Sn kg-1, w.w. According to our results, marbled electric ray could be considered as an ideal bioindicator of environmental pollution due to its ecological characteristics.

Tributyltin chloride induces chondrocyte damage through the activation of NLRP3­mediated inflammation and pyroptosis.

Tributyltin chloride (TBTC) is known to have effects and mechanisms in various diseases; however, whether TBTC is detrimental to joints and causes osteoarthritis (OA), as well as its underlying mechanism, has not yet been fully elucidated. The present study explored the effects of TBTC on rat chondrocytes, as well as on mouse OA. The toxicity of TBTC toward rat chondrocytes was detected using a lactate dehydrogenase (LDH) leakage assay and cell viability was evaluated using the Cell Counting Kit­8 assay. The results showed that TBTC decreased the viability of rat chondrocytes and increased the LDH leakage rate in a concentration­dependent manner. Moreover, compared with in the control group, TBTC increased the expression levels of interleukin (IL)­1ß, IL­18, matrix metalloproteinase (MMP)­1, MMP­13, NLR family pyrin domain containing 3 (NLRP3), caspase­1, PYD and CARD domain containing, and gasdermin D in chondrocytes. Furthermore, knockdown of NLRP3 reversed the TBTC­induced increases in LDH leakage and NLRP3 inflammasome­associated protein levels. In vivo, TBTC exacerbated cartilage tissue damage in mice from the OA group, as evidenced by the attenuation of safranin O staining. In conclusion, TBTC may aggravate OA in mice by promoting chondrocyte damage and inducing pyroptosis through the activation of NLRP3 and caspase­1 signaling. The present study demonstrated that TBTC can cause significant damage to the articular cartilage; therefore, TBTC contamination should be strictly monitored.

Microcosm study reveals the microbial and environmental effects on tributyltin degradation in an estuarine sediment.

Tributyltin (TBT) is one of the most harmful contaminants ever released into the aquatic environment. Despite being banned, it is still present at many locations throughout the world. Its degradation in sediment mainly occurs through microbial biodegradation, a process that remains unclear. This study therefore aimed at better understanding TBT biodegradation in estuarine sediment and the microbial community associated with it. Microcosm experiments were set up, embracing a range of environmental control parameters. Major community shifts were recorded, mainly attributed to the change in oxygen status. The highest percentage of degradation (36,8%) occurred at 4 °C in anaerobic conditions. These results are encouraging for the in-situ bioremediation of TBT contaminated muddy sediment in temperate ports worldwide. However, with TBT able to persist in the coastal environment for decades when undisturbed in anoxic sediment, further research is needed to fully understand the mechanisms that triggered this biodegradation observed in the microcosms.

Long-term tributyltin exposure alters behavior, oocyte maturation, and histomorphology of the ovary due to oxidative stress in adult zebrafish.

Tributyltin (TBT), an organotin endocrine-disrupting substance, is recognized as one of the important toxic environmental pollutants. The present study was carried out to investigate the toxic effects of TBT on behavior and the ovary of adult zebrafish with a focus on oxidative stress markers and oocyte maturation. Adult zebrafish were exposed to three different concentrations (125, 250, and 500 ng/L of water) of TBT for 28 days. TBT exposure produced a concentration-dependent negative effect on the body weight and behavior (anxiety-like symptoms) of adult zebrafish. Alterations in the activity of superoxide dismutase (SOD) and catalase (CAT), the total antioxidant capacity of ovarian tissue by the highest exposure level of TBT resulted in lipid peroxidation as indicated by increased malondialdehyde (MDA) level. The numbers of early-vitellogenic oocytes were significantly increased in zebrafish exposed to TBT as low as 125 ng/L. However, the numbers and size of fully-grown (mature) oocytes were significantly reduced in the highest exposure group only. Correlation between the MDA level and pre-vitellogenic oocytes in the 500 ng/L group indicated that lipid peroxidation prevented the maturation of pre-vitellogenic oocytes. TBT exposure produced significant histological changes in the ovary as evidenced by disturbed maturation of oocytes. In conclusion, TBT adversely affected the maturation of oocytes in zebrafish ovary through oxidative stress-mediated mechanisms.

Binding profiles of human and mouse complement component 8γ to trisubstituted organometallic compounds.

Complement component 8gamma (C8γ), a member of the lipocalin protein family, is suggested to act as a carrier protein for various chemicals. Although C8γ has been identified in both humans and rodents for some time, our understanding of the species differences in its chemical binding properties remains limited. In the present study, with the aim to elucidate the potential role of C8γ as a carrier protein in both humans and mice, we conducted a radioligand binding assay to examine the chemical binding properties of human C8γ (hC8γ) and mouse C8γ (mC8γ). Scatchard analysis revealed that [14C]TPT bound to hC8γ with an equilibrium dissociation constant (Kd) of 64.2 ± 32.4 nM, comparable to that of [14C]TPT to mC8γ. Competitive ligand-binding assays demonstrated binding of TPT and TBT to hC8γ, while diphenyltin, dibutyltin, monophenyltin, monobutyltin, and tetrabutyltin did not exhibit binding. These results suggest that for effective binding to C8γ, chemicals must possess substituents of appropriate bulkiness. Further analyses with other group 14 compounds with triphenyl substituents revealed that a central metal atom, rather than a central non-metal or semi-metal atom, is crucial for specific binding to both hC8γ and mC8γ. Overall our findings imply that C8γ may play a role in the physiological or toxicological actions of group 14 metal compounds with tributyl or triphenyl substituents by binding to these chemicals in both humans and mice.

Maternal exposure to tributyltin alters the breast milk, hormonal profile, and thyroid morphology of dams and induces sex-specific changes in neonate rat offspring.

Tributyltin (TBT) is the chemical substance commonly used worldwide to prevent biofouling of vessels. Due to its ability to bioaccumulate and biomagnify, even after being banned, significant concentrations of TBT can be detected in sediment, affecting marine and human life. Although studies have shown that direct exposure to TBT alters physiological parameters in mammals, the relationship between exposure to TBT during pregnancy and lactation, considered critical windows for metabolic programming, has not been fully elucidated. Our hypothesis is that offspring whose mothers were exposed to TBT during critical stages of development may exhibit dysfunctions in endocrine-metabolic parameters. We used pregnant Wistar rats that were divided into groups and received the following treatments from gestational day 7 until the end of lactation by intragastric gavage: vehicle (ethanol 0.01%; Control), low TBT dose (100 ng/kg of body weight (bw)/day; TBT100ng) and high TBT dose (1000 ng/kg bw/day; TBT1000ng). Dams and offspring at birth and weaning (21 days old) were studied. Maternal exposure to TBT promoted dose-dependent changes in dams. The findings for adiposity, milk composition and lipid profile were more pronounced in TBT100 ng dam; however, thyroid morphology was altered in TBT1000 ng dam. Female offspring were differentially affected by the dose of exposure. At birth, females in the TBT100ng group had low body weight, lower naso-anal length (NAL), and higher plasma T4, and at weaning, females in the TBT100ng group had lower insulin and leptin levels. Females in the TBT1000ng group had lower NAL at birth and lower leptinemia and weight of white adipose tissue at weaning. Male offspring from TBT groups showed high T3 at birth, without biometric alterations at birth or weaning. Despite these findings, both sexes exhibited dose-dependent morphological changes in the thyroid gland. Thus, maternal exposure to TBT constitutes an important route of contamination for both dams and offspring.

Tributyltin-induced oxidative stress causes developmental damage in the cardiovascular system of zebrafish (Danio rerio).

Tributyltin (TBT) can be used as an antifouling agent with anticorrosive, antiseptic and antifungal properties and is widely used in wood preservation and ship painting. However, it has recently been found that TBT can be harmful to aquatic organisms. In this study, to gain insight into the effects of TBT with respect to the development of the cardiovascular system in zebrafish embryos, zebrafish embryos were exposed to different concentrations of TBT solutions (0.2 µg/L, 1 µg/L, and 2 µg/L) at 2 h post-fertilization (hpf) TBT exposure resulted in decreased hatchability and heart rate, deformed features such as pericardial edema, yolk sac edema, and spinal curvature in zebrafish embryos, and impaired heart development. Expression of cardiac development-related genes (vmhc, myh6, nkx2.5, tbx5a, gata4, tbx2b, nppa) is dysregulated. Transgenic zebrafish Tg (fli1: EGFP) were used to explore the effects of TBT exposure on vascular development. It was found that TBT exposure could lead to impaired development of intersegmental vessels (ISVs), common cardinal vein (CCV), subintestinal vessels (SIVs) and cerebrovascular. The expression of vascular endothelial growth factor (VEGF) signaling pathway-related genes (flt1, flt4, kdr, vegfa) was downregulated. Biochemical indices showed that ROS and MDA levels were significantly elevated and that SOD and CAT activities were significantly reduced. The expression of key genes for prostacyclin synthesis (pla2, ptgs2a, ptgs2b, ptgis, ptgs1) is abnormal. Therefore, it is possible that oxidative stress induced by TBT exposure leads to the blockage of arachidonic acid (AA) production in zebrafish embryos, which affects prostacyclin synthesis and consequently the normal development of the heart and blood vessels in zebrafish embryos.

Whole-Transcriptome Analysis Reveals the RNA Profiles in Mouse Bone Marrow Mesenchymal Stem Cells or Zebrafish Embryos After Exposure to Environmental Level of Tributyltin.

To understand the underlying molecular mechanisms, mouse bone marrow mesenchymal stem cells (BMSCs) and zebrafish embryos were exposed to the control group and Tributyltin (TBT) group (10 ng/L, environmental concentration) for 48 h, respectively. The expression profiles of RNAs were investigated using whole-transcriptome analysis in mouse BMSCs or zebrafish embryos after TBT exposure. For mouse BMSCs, the results showed 2,449 differentially expressed (DE) mRNAs, 59 DE miRNAs, 317 DE lncRNAs, and 15 circRNAs. Similarly, for zebrafish embryos, the results showed 1,511 DE mRNAs, 4 DE miRNAs, 272 DE lncRNAs, and 28 circRNAs. According to KEGG pathway analysis showed that DE RNAs were mainly associated with immune responses, signaling, and cellular interactions. Competing endogenous RNA (ceRNA) network analysis revealed that the regulatory network of miRNA-circRNA constructed in zebrafish embryos was more complex compared to that of mouse BMSCs.

Toxic Relationships: Prediction of TBT's Affinity to the Ecdysteroid Receptor of Triops longicaudatus.

Tributyltin (TBT) is a biocide introduced in the 1960s in antifouling paints. Despite legislation banning its use, its persistence in the environment still causes significant harm to organisms. Tributyltin is a ligand of retinoid X receptors (RXR) and ecdysteroid receptors (EcRs), which in arthropods act as homologs of RXR. Focusing on Metazoan species, this study used genomic and proteomic information from different sources to compare their three-dimensional structure, phylogenetic distribution, and amino acid sequence alterations. The objective was to identify possible patterns that relate organisms' sensitivity to TBT using the species Triops longicaudatus as the basis for the comparisons. The results showed great conservation of this protein across several species when comparing the interaction amino acids described to RXR (an EcR analog) in Homo sapiens. The three-dimensional comparison of RXR showed little conformational variation between different sequences by maintaining the interaction pocket. As for the Species Sensitivity Distribution (SSD) curve, an HC05 = 0.2649 [0.0789-0.7082] µg/L was obtained with no specific distribution between the different taxa. Protein-ligand docking analysis was then used to confirm the SSD curve ranking of species. Still, the results showed an opposite trend that may be related, for example, to differences in the LC50 values used in the calculations. This study serves as the first step for applying bioinformatics techniques to produce information that can be used as an alternative to animal or cellular experimentation. These techniques could be adapted to various chemicals and proteins, allowing for observations in a shorter timeframe and providing information on a broader spectrum.

Factors affecting the accumulation of organotins by wild fish: A case study in the Three Gorges Reservoir, China.

Organotin compounds (OTs) accumulate in fish easily, however, research on their influencing factors is still limited. This study collected 25 species of fish with different diets, habitats, and age from the Three Gorges Reservoir (TGR), the largest deep-water river channel-type reservoir in China, and analyzed the accumulation characteristics of OTs in these fish. The results showed that tributyltin (TBT) and triphenyltin (TPhT) were the dominant OTs in fish from the TGR. The correlation between OTs concentration and age, body length, and body weight varied with fish species. The concentrations of TBT and TPhT in carnivorous fish (mean, 25.78 and 11.69 ng Sn/g dw, respectively) were higher than those in other diet fish (P<0.01), but there was no significant difference in fish at different habitat water layers (P>0.05). In addition, the degradation rates of TBT and TPhT in different fish species were all below 50%. In summary, the accumulation of TBT and TPhT in fish is mainly influenced by diet, and both TBT and TPhT were difficult to degrade in fish. These results reveal the pollution characteristics of OTs in fish from the TGR, and can improve our understanding of the factors influencing TBT and TPhT accumulation in freshwater fish.

Effects of Tributyltin-Contaminated Aquatic Environments and Remediated Water on Early Development of Sea Urchin (Hemisentrotus pulcherrimus).

In this study, gametotoxicity and embryotoxicity experiments were performed using Hemicentrotus pulcherrimus to investigate the toxic effects of tributyltin (TBT). The effects of TBT on fertilization and embryogenesis were assessed at various concentrations (0, 0.02, 0.05, 0.09, 0.16, 0.43, 0.73, 4.68, and 9.22 ppb). The fertilization rates decreased in a concentration-dependent manner, with significant reduction following treatment with TBT at 0.05 ppb. Embryos exhibited developmental impairment after TBT exposure at each tested concentration. The frequency of developmental inhibition delay that treatment with TBT delayed embryonic development in a dose-dependent manner, with 100% of embryos exhibiting developmental impairment at 4.68 ppb. During developmental recovery tests, embryos cultured in fresh media without TBT showed advanced embryonic development. Although the observed normal development after transferring the developmentally delayed embryos to fresh media without TBT offers prospects for the restoration of contaminated environments, embryonic development remained incomplete. These results suggest that TBT adversely affects the early embryonic development of H. pulcherrimus.

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

Tributyltin (TBT) is an environmental contaminant present on all continents, including Antarctica, with a potent biocidal action. Its use began to be intensified during the 1960s. It was effectively banned in 2003 but remains in the environment to this day due to several factors that increase its half-life and its misuse despite the bans. In addition to the endocrine-disrupting effect of TBT, which may lead to imposex induction in some invertebrate species, there are several studies that demonstrate that TBT also has an immunotoxic effect. The immunotoxic effects that have been observed experimentally in vertebrates using in vitro and in vivo models involve different mechanisms; mainly, there are alterations in the expression and/or secretion of cytokines. In this review, we summarize and update the literature on the impacts of TBT on the immune system, and we discuss issues that still need to be explored to fill the knowledge gaps regarding the impact of this endocrine-disrupting chemical on immune system homeostasis.

Endoplasmic Reticulum Stress and Autophagy Are Involved in Hepatotoxicity Induced by Tributyltin.

Tributyltin (TBT), a common contaminant in aquatic ecosystems, has severe toxic effects on multiple tissues and organs, especially the liver. Previous toxicogenomic analysis has indicated that the main mechanism of TBT-induced hepatotoxicity is related to the activation of the apoptotic pathway. However, the mechanism of action occurring before the activation of apoptosis is still unclear. Herein, we applied proteomic technology to explore the protein expression profile of TBT-treated HL7702 normal human liver cells. The ultrastructural changes in cells were observed by transmission electron microscopy. After low dose (2 µΜ) TBT treatment, activation of the unfolded protein response and endoplasmic reticulum stress were observed; the expression levels of PERK, ATF6, BiP, and CHOP were significantly elevated, and splicing of XBP1 mRNA was initiated. When the TBT concentration increased to 4 µΜ, the protein levels of Beclin1, Atg3, Atg5, Atg7, and Atg12-Atg5 were significantly elevated, and the protein level of LC3Ⅰ decreased while that of LC3Ⅱ increased, suggesting the activation of autophagy. As the TBT concentration continued to increase, autophagy could not eliminate the damage, and apoptosis eventually occurred. These results indicate novel pathways of hepatotoxicity induced by TBT and provide insights for future studies.

Lipid accumulation and gene expression changes induced by tributyltin exposure in primary hepatocytes of lined seahorse (Hippocampus erectus).

Tributyltin (TBT), an antifouling biocide frequently detected in aquatic systems, is generally considered to be an environmental obesogen. However, alterations in lipid metabolism in aquatic animals that are exposed to TBT are scarcely known. This study examined the effects of in vitro exposure to TBT on hepatic lipid homeostasis in the lined seahorse (Hippocampus erectus). Primary seahorse hepatocyte cultures were established for the first time. TBT exposure (100 and 500 nM for 24 h) significantly promoted lipid accumulation in seahorse hepatocytes and drastically reduced the number of active intracellular lysosomes. Furthermore, exposure to TBT significantly upregulated the gene expression of lipogenic enzymes and transcription factors but downregulated that of genes involved in the catabolism of lipid droplets in seahorse hepatocytes. These results indicate that TBT disrupts hepatic lipid homeostasis by simultaneously promoting lipid synthesis and inhibiting lipid droplet breakdown in seahorses. The present study extends our understanding of the utilization of primary hepatocytes from marine animals for toxicological research, and the molecular evidence of the effects of TBT on hepatic lipid homeostasis in teleost fishes.

The possible ameliorative role of Lycopene on Tributyltin induced thyroid damage in adult male albino rats (histological, immunohistochemical and biochemical study).

Tributyltin is used in industrial applications. This current research aimed to study the effect of Tributyltin on the thyroid gland structure and function of adult male albino rats and the protective effect of Lycopene. Twenty-one male adult albino rats were classified into three groups: Control, treated that received Tributyltin, and protective that received Lycopene with Tributyltin. At the end of the experiment, blood samples were collected and T4, T3, and (TSH) were measured. Tissue superoxide dismutase (SOD) and malondialdehyde (MDA) were estimated. Thyroid gland specimens were processed for histological and immunohistochemical examination. Then morphometric and statistical analyses were done. The treated group showed affection in thyroid function and histological structure as vacuolated colloid and cytoplasm and dark nuclei. Ultrastructurally, follicular cells showed irregular shrunken nuclei, atrophied apical microvilli, vacuoles, multiple lysosomal granules, mitochondria with destructed cristae, and extensively dilated rough endoplasmic reticulum. There was increase in Caspase-3 immunoexpression and decrease in Beclin-1 immunoexpression. The thyroid structure and biochemical markers improved after Lycopene administration. The thyroid gland damage caused by Tributyltin is ameliorated by Lycopene.