Evaluation of Lipids and Lipid-Related Transcripts in Human and Ovine Theca Cells and an in Vitro Mouse Model Exposed to the Obesogen Chemical Tributyltin.

BACKGROUND: Exposure to obesogenic chemicals has been reported to result in enhanced adipogenesis, higher adipose tissue accumulation, and reduced ovarian hormonal synthesis and follicular function. We have reported that organotins [tributyltin (TBT) and triphenyltin (TPT)] dysregulate cholesterol trafficking in ovarian theca cells, but, whether organotins also exert lipogenic effects on ovarian cells remains unexplored. OBJECTIVE: We investigated if environmentally relevant exposures to organotins [TBT, TPT, or dibutyltin (DBT)] induce lipid dysregulation in ovarian theca cells and the role of the liver X receptor (LXR) in this effect. We also tested the effect of TBT on oocyte maturation and neutral lipid accumulation, and lipid-related transcript expression in cumulus cells and preimplantation embryos. METHODS: Primary theca cell cultures derived from human and ovine ovaries were exposed to TBT, TPT, or DBT (1, 10, or 50 ng/ml). The effect of these chemical exposures on neutral lipid accumulation, lipid abundance and composition, lipid homeostasis-related gene expression, and cytokine secretion was evaluated using liquid chromatography-mass spectrometry (LC-MS), inhibitor-based methods, cytokine secretion, and lipid ontology analyses. We also exposed murine cumulus-oocyte complexes to TBT and evaluated oocyte maturation, embryo development, and lipid homeostasis-related mRNA expression in cumulus cells and blastocysts. RESULTS: Exposure to TBT resulted in higher intracellular neutral lipids in human and ovine primary theca cells. In ovine theca cells, this effect was dose-dependent, independent of cell stage, and partially mediated by LXR. DBT and TPT resulted in higher intracellular neutral lipids but to a lesser extent in comparison with TBT. More than 140 lipids and 9 cytokines were dysregulated in TBT-exposed human theca cells. Expression of genes involved in lipogenesis and fatty acid synthesis were higher in theca cells, as well as in cumulus cells and blastocysts exposed to TBT. However, TBT did not impact the rates of oocyte maturation or blastocyst development. DISCUSSION: TBT induced dyslipidemia in primary human and ovine theca cells, which may be responsible for some of the TBT-induced fertility dysregulations reported in rodent models of TBT exposure. https://doi.org/10.1289/EHP13955.

Novel triphenyltin(IV) compounds with carboxylato N-functionalized 2-quinolones as promising potential anticancer drug candidates: in vitro and in vivo evaluation.

Three newly synthesized triphenyltin(IV) compounds, Ph3SnL1 (L1- = 3-(4-methyl-2-oxoquinolin-1(2H)-yl)propanoato), Ph3SnL2 (L2- = 2-(4-methyl-2-oxoquinolin-1(2H)-yl)ethanoato), and Ph3SnL3 (L3- = 2-(4-hydroxy-2-oxoquinolin-1(2H)-yl)ethanoato), were characterized by elemental microanalysis, FT-IR spectroscopy and multinuclear (1H, 13C and 119Sn) NMR spectroscopy. A single X-ray diffraction study indicates that compounds Ph3SnL1 and Ph3SnL2 exhibit a 1D zig-zag chain polymeric structure, which in the case of Ph3SnL2 is additionally stabilized by π-interactions. In addition, the synthesized compounds were further examined using density functional theory and natural bond orbital analysis. The compounds have been evaluated for their in vitro anticancer activity against three human cell lines: MCF-7 (breast adenocarcinoma), A375 (melanoma), HCT116 (colorectal carcinoma), and three murine cell lines: 4T1 (breast carcinoma), B16 (melanoma), CT26 (colon carcinoma) using MTT and CV assays. The IC50 values fall in the nanomolar range, indicating that these compounds possess better anticancer activity than cisplatin. The study of the effect of the newly developed drug Ph3SnL1 showed its plasticity in achieving an antitumor effect in vitro, which depends on the specificity of the phenotype and the redox status of the malignant cell line and ranges from the initiation of apoptotic cell death to the induction of differentiation to a more mature cell form. In the syngeneic model of murine melanoma, Ph3SnL1 showed the potential to reduce the tumor volume similar to cisplatin, but in a well-tolerated form and with low systemic toxicity, representing a significant advantage over the conventional drug.

Triphenyltin induced darker body coloration by disrupting melanocortin system and pteridine metabolic pathway in a reef fish, Amphiprion ocellaris.

Triphenyltin (TPT) is a typical persistent organic pollutant whose occurrence in coral reef ecosystems may threaten the survival of reef fishes. In this study, a brightly colored representative reef fish, Amphiprion ocellaris was used to explore the effects of TPT at environmental levels (1, 10, and 100 ng/L) on skin pigment synthesis. After the fish were exposed to TPT for 60 days, the skin became darker, owing to an increase in the relative area of black stripes, a decrease in orange color values while an increase in brown color values, and an increase in the number of melanocytes in the orange part of the skin tissues. To explore the mechanisms by which TPT induces darker body coloration, the enzymatic activity and gene expression levels of the members of melanocortin system that affect melanin synthesis were evaluated. Leptin levels and lepr expression were found to be increased after TPT exposure, which likely contributed to the increase found in pomc expression and α-melanocyte-stimulating hormone (α-MSH) levels. Then Tyr activity and mc1r, tyr, tyrp1, mitf, and dct were upregulated, ultimately increasing melanin levels. Importantly, RT-qPCR results were consistent with the transcriptome analysis of trends in lepr and pomc expression. Because the orange color values decreased, pterin levels and the pteridine metabolic pathway were also evaluated. The results showed that TPT induced BH4 levels and spr, xdh, and gch1 expression associated with pteridine synthesis decreased, ultimately decreasing the colored pterin content (sepiapterin). We conclude that TPT exposure interferes with the melanocortin system and pteridine metabolic pathway to increase melanin and decrease colored pterin levels, leading to darker body coloration in A. ocellaris. Given the importance of body coloration for the survival and reproduction of reef fishes, studies on the effects of pollutants (others alongside TPT) on body coloration are of high priority.

Transcriptomics-based analysis reveals the nephrotoxic effects of triphenyltin (TPT) on SD rats by affecting RAS, AQPs and lipid metabolism.

Triphenyltin (TPT) is a class of organotin compounds that are extensively used in industry and agriculture. They have endocrine-disrupting effects and cause severe environmental contamination. Pollutants may accumulate in the kidneys and cause pathological complications. However, the mechanism of TPT's toxicological effects on the kidney remains unclear. This study aimed to investigate the toxic effects and mechanism of action of TPT exposure on renal impairment in rats. Male SD rats were divided into four groups: the Ctrl group (control group), TPT-L group (0.5 mg/kg/d), TPT-M group (1 mg/kg/d), and TPT-H group (2 mg/kg/d). After 28 days of exposure to TPT, we observed the morphology and structure of kidney tissue using HE, PASM, and Masson staining. We also detected serum biochemical indexes, performed transcriptome sequencing of rat kidney tissue using RNA-seq. Furthermore, protein expression levels were measured through immunohistochemistry and gene expression levels were determined using RT-qPCR. The study results indicated a decrease in kidney weight and relative kidney weight after 28 days of exposure to TPT. Additionally, TPT caused damage to kidney structure and function, as evidenced by HE staining, PASM staining, and serum biochemical tests. Transcriptomics identified 352 DEGs, and enrichment analyses revealed that TPT exposure primarily impacted the renin-angiotensin system (RAS). The expression levels of water channel proteins were reduced, and the expression levels of RAS and lipid metabolism-related genes (Mme, Ace, Fasn, Cyp4a8, Cpt1b and Ppard) were significantly decreased in the TPT-treated group. In summary, exposure to TPT may impair renal structure and function in rats by affecting RAS, AQPs, and lipid metabolism.

Fecal transplantation of young mouse donors effectively improves enterotoxicity in elderly recipients exposed to triphenyltin.

Triphenyltin (TPT) is a widely used biocide known for its high toxicity to various organisms, including humans, and its potential contribution to environmental pollution. The aging process leads to progressive deterioration of physiological functions in the elderly, making them more susceptible to the toxic effects of environmental pollutants. This study aimed to investigate the mitigating effect of fecal transplantation in young mice on the toxicological impairment caused by TPT exposure. For the study, 18-month-old mice were divided into four groups with six replicates each. The control group was fed a basal diet, the TPT group was exposed to 3.75 mg/Kg TPT, the feces group received fecal transplantation from 8-week-old young mice, and the combined group was exposed to 3.75 mg/Kg TPT after receiving fecal transplantation. Compared with the elderly control group, TPT induced significant upregulation of mRNA expression of pro-inflammatory factors (IL-1ß, IL-6, TNF-α), while the anti-inflammatory factor gene IL-10 was significantly suppressed. The mRNA expression of intestinal barrier proteins (Claudin, Occludin, Muc2) was also significantly downregulated. However, fecal transplantation in young mice alleviated TPT-induced changes in inflammatory factors, ameliorated oxidative stress, and increased the activities of antioxidant enzymes (including SOD, CAT, GSH-Px). Further analysis using 16 s RNA showed that exposure to TPT led to changes in the composition of the intestinal flora. Untargeted metabolomics observations of feces from older mice revealed that exposure to TPT resulted in altered fecal metabolites. Fecal transplantation in young mice altered the microbiota of TPT-exposed older mice, especially by enhancing the levels of core probiotics. Similar beneficial effects were observed through untargeted metabolomics. Overall, this study highlights the potential benefits of young fecal transplantation in protecting the elderly from the toxicity of TPT, offering a promising approach to improve healthy aging.

Update on the status of the contamination by organotin compounds in sediment of Nuevo Gulf, Argentina. Insights from field and experimental studies.

Organotin compounds are persistent pollutants and are considered chemicals of high environmental concern. In the present study, the distribution and degradation of tributyltin were evaluated in field sediments and through an ex situ experiment. For this, sediment samples from two locations were analysed: Luis Piedrabuena Harbour, with higher maritime traffic, and Cerro Avanzado, which receives less impact from anthropogenic activities. The results indicated that pollution levels at Luis Piedrabuena Harbour have decreased compared with studies performed 9 years ago for the same area. On the contrary, traces of organotin compounds have been found for the first time at Cerro Avanzado. Moreover, the butyltin degradation index indicated that organotin compounds undergo an advanced degradation process in the collected samples at both sites. Ex situ experiments revealed a limited capacity of sediments to retain tributyltin, and suggested an active role of bioturbation activity in the degradation of these compounds. In addition, visualisation using chemometric techniques (principal components analysis) allowed a simpler analysis of two sediment characteristics: the degree of contamination and the degradation levels of organotin compounds.

Occupational exposure to organotin substances: Development of a liquid chromatographic separation method for 11 organotin compounds in workplace air samples via HPLC-ICP-MS.

Organotin compounds (OTCs) are widely regulated but rank among the most used organometallic compounds in various industrial sectors. They are significantly more toxic than inorganic tin compounds. At workplaces, OTCs can be released as vapors or dust particles and can be absorbed by inhalation or skin contact. Occupational exposure thus represents a great risk for the absorption of OTCs for employees. Methods for OTCs speciation in workplace air monitoring currently do not exist. This study describes the development of a separation method for eleven in Germany regulated OTCs via HPLC-ICP-MS. The method allows a near baseline separation of MMT, MBT, MOT, MPhT, DMT, DBT, DPhT, TMT, TBT, TPhT and TTMT within 22 min on a C18 column and a ternary solvent and flow rate gradient using methanol, acetonitrile, and ultrapure water + 6% (v/v) acetic acid + 0.17% (m/v) α-tropolone. Ten analytes show linearity in the working range of 10 - 100 µg OTCs/L with R² > 0.999. Due to its high volatility the analyte TTMT showed a quadratic relationship between concentration and signal intensity with R² = 0.9998. The determination of the instrumental limits resulted in detection limits between 0.14 and 0.57 µg Sn/L and limits of quantification between 0.49 and 1.97 µg Sn/L. Over the course of this study thermal instability and cross reactivity of OTC in solution became apparent. Formation of two reaction products in mixed OTCs solutions have been observed. These effects will further be examined within development of appropriate sampling and sample preparation for workplace air to provide a suitable method for the determination of OTCs at workplaces according to normative references.

TMT-based quantitative proteomics analysis of Sprague-Dawley rats liver reveals Triphenyltin induced liver damage and lipid metabolism disorders.

Triphenyltin (TPT) is a widely used pesticide that has a negative impact on biological health and production efficiency. In addition, TPT poses a threat to human health through the food chain and environmental pollution. However, the exact mechanism of TPT toxicity remains unclear. In this study, we investigated the hepatotoxicity of TPT and its effects on lipid metabolism using male SD rats as an animal model. Our results from HE and serum biochemical analysis suggested that TPT could damage liver structure and function, resulting in disruption of lipid metabolism. We therefore proceeded to analyze the proteomic response of rat liver tissue after 28 days of treatment with 2 mg/kg/d TPT. Our study demonstrates that TPT has a variety of effects on liver protein expression in rats. Through bioinformatic analysis, we observed significant changes in proteins related to fatty acid oxidation and synthesis due to TPT exposure. Furthermore, western blot and RT-qPCR experiments confirmed that TPT can affect lipid metabolism through the PPAR pathway. These findings suggest that TPT exposure can lead to liver damage, lipid accumulation and metabolic disorders.

Micro(nano)plastics in marine medaka: Entry pathways and cardiotoxicity with triphenyltin.

The simultaneous presence of micro(nano)plastics (MNPs) and pollutants represents a prevalent environmental challenge that necessitates understanding their combined impact on toxicity. This study examined the distribution of 5 µm (PS-MP5) and 50 nm (PS-NP50) polystyrene plastic particles during the early developmental stages of marine medaka (Oryzias melastigma) and assessed their combined toxicity with triphenyltin (TPT). Results showed that 2 mg/L PS-MP5 and PS-NP50 could adhere to the embryo surface. PS-NP50 can passively enter the larvae and accumulate predominantly in the intestine and head, while PS-MP5 cannot. Nonetheless, both types can be actively ingested by the larvae and distributed in the intestine. 2 mg/L PS-MNPs enhance the acute toxicity of TPT. Interestingly, high concentrations of PS-NP50 (20 mg/L) diminish the acute toxicity of TPT due to their sedimentation properties and interactions with TPT. 200 µg/L PS-MNPs and 200 ng/L TPT affect complement and coagulation cascade pathways and cardiac development of medaka larvae. PS-MNPs exacerbate TPT-induced cardiotoxicity, with PS-NP50 exhibiting stronger effects than PS-MP5, which may be related to the higher adsorption capacity of NPs to TPT and their ability to enter the embryos before hatching. This study elucidates the distribution of MNPs during the early developmental stages of marine medaka and their effects on TPT toxicity, offering a theoretical foundation for the ecological risk assessment of MNPs.

Perinatal exposure to the immune-suppressant di-n-octyltin dichloride affects brain development in rats.

Disruption of the immune system during embryonic brain development by environmental chemicals was proposed as a possible cause of neurodevelopmental disorders. We previously found adverse effects of di-n-octyltin dichloride (DOTC) on maternal and developing immune systems of rats in an extended one-generation reproductive toxicity study according to the OECD 443 test guideline. We hypothesize that the DOTC-induced changes in the immune system can affect neurodevelopment. Therefore, we used in-vivo MRI and PET imaging and genomics, in addition to behavioral testing and neuropathology as proposed in OECD test guideline 443, to investigate the effect of DOTC on structural and functional brain development. Male rats were exposed to DOTC (0, 3, 10, or 30 mg/kg of diet) from 2 weeks prior to mating of the F0-generation until sacrifice of F1-animals. The brains of rats, exposed to DOTC showed a transiently enlarged volume of specific brain regions (MRI), altered specific gravity, and transient hyper-metabolism ([18F]FDG PET). The alterations in brain development concurred with hyper-responsiveness in auditory startle response and slight hyperactivity in young adult animals. Genomics identified altered transcription of key regulators involved in neurodevelopment and neural function (e.g. Nrgrn, Shank3, Igf1r, Cck, Apba2, Foxp2); and regulators involved in cell size, cell proliferation, and organ development, especially immune system development and functioning (e.g. LOC679869, Itga11, Arhgap5, Cd47, Dlg1, Gas6, Cml5, Mef2c). The results suggest the involvement of immunotoxicity in the impairment of the nervous system by DOTC and support the hypothesis of a close connection between the immune and nervous systems in brain development.

Exposure to triphenyltin impairs gut integrity, disturbs gut microbiota, and alters fecal metabolites.

Triphenyltin is an environmental contaminant widely used in antifouling paints and can cause toxicity in various organs in living organisms. However, its effects on intestinal function and the microbiome of the gut remain unknown. The objective of this study was to explore the intestinal toxicity of triphenyltin in mice by orally administering 0, 1.875, 3.75, and 7.5 mg/Kg to adult male mice for 8 weeks. Results showed that triphenyltin caused ileum tissue damage, induced oxidative stress, upregulated inflammation-related gene expression and increased serum tumor-necrosis factor α (TNF-α) levels in mice. Triphenyltin impaired ileum barrier function by downregulating Muc2, ZO-1, Occludin and their protein levels at 3.75 and 7.5 mg/Kg. TPT exposure led to partial inflammation and decreased mucin mRNA expression in the colon. Triphenyltin altered intestinal micro-ecological balance and fecal metabolome in mice. In conclusion, triphenyltin alters the mouse gut microbiota and fecal metabolome.

Determination of organotin compounds in marine sediments from Arctic Svalbard and West Antarctic Fildes Peninsula.

This study investigated the contamination levels of five typical organotin compounds in Arctic and Antarctic marine sediments. Organotin total concentrations ranged from not detected (ND) to 37.9 ng Sn/g dw and from ND to 34.0 ng Sn/g dw in surface sediments of Svalbard and Fildes Peninsula, respectively. Dibutyltin accounted for 11.3 %-100 % of butyltins in Arctic sediments, whilst diphenyltin was the predominant phenyltin species in both Arctic and Antarctic. However, the concentrations of tributyltin and triphenyltin were lower than low-substituted organotins in the study areas, indicating the effectiveness of international ban on the use of triorganotin-based antifouling paints. No significant difference in organotin contamination was found between Arctic and Antarctic, although the time suffered from human interference was shorter in the Antarctic. Overall, these data can provide a diagnosis of recent organotin inputs in polar regions and serve as a baseline for future study assessing their local applications.

Synthesis, characterization and discovery of multiple anticancer mechanisms of dibutyltin complexes based on salen-like ligands.

A series of novel dibutyltin complexes based on salen-like ligands (S01-S03) were synthesized and characterized using ultraviolet-visible spectra，infrared spectra, 1H, 13C, and 119Sn nuclear magnetic resonance, high-resolution mass spectrometry, X-ray crystallography, and thermogravimetric analysis. Complex S03 had excellent anticancer activity in vitro (IC50 = 1.5 ± 0.2 µM in CAL-27 cell lines), which highly activated ROS expression levels and induced apoptosis and cell cycle arrest at the G2/M phase. Interestingly, complex S03 induced cancer cell death through multiple mechanisms (mitochondrial pathway, ER-stress pathway, and DNA damage pathway). This study reveals new mechanisms of organotin complexes and provides new insights into the development of organotin metal complexes as anticancer drugs in the future, and compounds with multiple anticancer mechanisms may be a new strategy for delaying or overcoming drug resistance to chemotherapy and target therapy.

Cellular and DNA Toxicity Study of Triphenyltin Ethyl Phenyl Dithiocarbamate and Triphenyltin Butyl Phenyl Dithiocarbamate on K562, Leukemia Cell Line.

INTRODUCTION: Continuous research for new effective drugs to treat cancer has improved our understanding on the mechanism of action of these drugs and paved new potential for their application in cancer treatments. In this study, organotin compounds known as triphenyltin ethyl phenyl dithiocarbamate and triphenyltin butyl phenyl dithiocarbamate were investigated for their toxicity on leukemia cell line (K562) and non-cancerous cell line (Chang liver cell and lung fibroblast, V79 cell). METHODS: MTT assay was performed to evaluate the cytotoxic effects of both compounds toward the cells after 24, 48 and 72 hours of exposure or treatment. The alkaline comet assay was conducted to determine the DNA damage on K562 cells after been exposed to both compounds for 30, 60 and 90 minutes. RESULTS: The IC50 values obtained from K562 cells ranged from 0.01 to 0.30 µM, whereas for both Chang liver cell and lung fibroblast V79 cell, the values ranged from 0.10 to 0.40 µM. For genotoxicity evaluation, the percentage of damaged DNA is measured as an average of tail moment, and was found to be within 1.20 to 2.20 A.U while the percentage of DNA intensity ranging from 1.50 to 3.50% indicating no genotoxic effects. CONCLUSION: Both compounds are cytotoxic toward leukemia cells and non-cancerous cells but do not exert their genotoxic effects towards leukemia cell.

Trigonelline Chloride Ameliorated Triphenyltin-Induced Testicular Autophagy, Inflammation, and Apoptosis: Role of Recovery.

Triphenyltin chloride (TPT-Cl) is an organometallic organotin. This study aimed to investigate the role of trigonelline (TG) along with the impact of TPT withdrawal on the testicular toxicity induced by TPT-Cl. Thirty-six adult male albino rats were divided into control, TG (40 mg/kg/day), TPT-Cl (0.5 mg/kg/day), TG + TPT-Cl, and recovery groups. Animals were daily gavaged for 12 weeks. Both TG and TPT-Cl withdrawal improved TPT-Cl-induced testicular toxicity features involving testis and relative testis weight reduction, luteinizing hormone, follicular stimulating hormone, and sex hormone-binding globulin elevation, reduction of inhibin B, free testosterone levels, and sperm count reduction with increased abnormal sperm forms. Moreover, both TG and TPT-Cl withdrawal reduced inflammatory activin A, follistatin, tumor necrosis factor α, interleukin-1ß, and proapoptotic Bax and elevated antiapoptotic Bcl2 in testicular tissues mediated by TPT-Cl. TG and TPT-Cl withdrawal restored the excessive autophagy triggered by TPT-Cl via elevation of mTOR, AKT, PI3K, and P62/SQSTM1 and reduction of AMPK, ULK1, Beclin1, and LC3 mRNA gene expressions and regained the deteriorated testicular structure. In conclusion, TG and TPT-Cl withdrawal had an ameliorative role in partially reversing TPT-Cl-induced testicular toxicity. However, the findings indicated that the use of TG as an adjunctive factor is more favorable than TPT-Cl withdrawal, suggesting the capability of the testis for partial self-improvement.

Occurrence of organotin compounds in food: increasing challenge of phenyltin compounds.

Concentrations and distribution for 16 organotin compounds were studied in all kinds of foods, including seafood, agricultural products, and wine. Meanwhile, the degradation of the TBT or TPhT was also evaluated. Concentrations of total organotins in seafood, agricultural products, and wine were 1047.2, 469.4, and 13.5 µg Sn/kg. Meanwhile, the most frequently detected organotin in three kinds of samples were TPhT, MPhT, and MPhT, respectively. The results demonstrated that phenyltin may probably become an emerging organotin pollutant. Regarding seafood, organotin concentrations of fish and mollusks were much higher than those of crustaceans. At the same time, a significant positive correlation was observed between the concentrations of TBT and MBT (p < 0.05), and between DBT and MBT(p < 0.0001). Moreover, TPhT was significantly and positively associated with DPhT (p < 0.0001), suggesting that TPhT was the precursor of DPhT. Apart from the likely illegal use of OTs as biocides in antifouling paints for ships, anthropogenic activity like agricultural activity or industrial activity also caused organotin contamination. Further research and more effective measures should be formulated to protect the food safety. Meanwhile, monitoring of the organotin contamination should not only in Qinhuangdao, but also expand to the cities along Bohai Bay.

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.

Trimethyltin chloride exposure induces apoptosis and necrosis and impairs islet function through autophagic interference.

Trimethyltin chloride (TMT) is a highly toxic organotin compound often used in plastic heat stabilizers, chemical pesticides, and wood preservatives. TMT accumulates mainly through the environment and food chain. Exposure to organotin compounds is associated with disorders of glucolipid metabolism and obesity. The mechanism by which TMT damages pancreatic tissue is unclear. For this purpose, a subacute exposure model of TMT was designed for this experiment to study the mechanism of damage by TMT on islet. The fasting blood glucose and blood lipid content of mice exposed to TMT were significantly increased. Histopathological and ultrastructural observation and analysis showed that the TMT-exposed group had inflammatory cell infiltration and necrosis. Then, mouse pancreatic islet tumour cells (MIN-6) were treated with TMT. Autophagy levels were detected by fluorescence microscopy. Real-time quantitative polymerase chain reaction and Western blotting were used for verification. A large amount of autophagy occurred at a low concentration of TMT but stagnated at a high concentration. Excessive autophagy activates apoptosis when exposed to low levels of TMT. With the increase in TMT concentration, the expression of necrosis-related genes increased. Taken together, different concentrations of TMT induced apoptosis and necrosis through autophagy disturbance. TMT impairs pancreatic (islet ß cell) function.

Short-term triphenyltin exposure alters microbial homeostasis in the silkworm (Bombyx mori) midgut.

Triphenyltin (TPT) is a widespread synthetic chemical used in many fields and its potential risk to organisms has been comprehensively investigated using different animal models and species. Currently, little is known about the effects of TPT exposure on microbial midgut diversity, therefore we explored these effects in the lepidopterous silkworm model using 16S rDNA sequencing. In total, 5273 and 5065 operational taxonomic units (OTUs) were identified in control and TPT-exposure group samples, ranging from 424 to 728 OTUs/sample. Alpha-diversity analyses revealed that TPT exposure induced the fluctuations of gut microbial diversity and abundance while beta-diversity analyses identified a distinct impact on major gut microbiota components. In our microbiome analyses, 23 phyla and 353 genera were recognized in the control group, while 20 phyla and 358 genera were recognized in the TPT exposure group. At the genus level, midgut microbiota were composed of several predominant bacterial genera, including Muribaculaceae, Lactobacillus, and UCG-010. In the TPT exposure group, o__Bacillales, f__Bacillaceae, and f__Caldicoprobacteraceae abundance was relatively high, while f__Oscillospiraceae, f__Fusobacteriaceae, and f__SC_I_84 abundance was relatively high in the control group. Gene function analyses in silkworm microbiota after TPT exposure showed that biosynthesis of ansamycins, fructose and mannose metabolism, glycerolipid metabolism, type II diabetes mellitus, glycolysis/gluconeogenesis, lipid metabolism, translation proteins, atrazine degradation, DNA repair and recombination proteins, nicotinate and nicotinamide metabolism were significantly increased. Collectively, our silkworm model identified gut microbial diversity risks and the adverse effects from TPT exposure, which were similar to other aquatic animals. Therefore, TPT levels in environmental samples must be monitored to prevent ecological harm.

Recent advancements of fluorescent tin(IV) complexes in biomedical molecular imaging.

In the last few years, tin(IV) complexes have emerged as very attractive candidates in the field of molecular imaging due to their unique photophysical properties. Despite the few reviews published to date covering the chemistry of organotin and tin complexes and their cytotoxic potential, there are no reviews devoted to their live cell imaging properties. Therefore, this feature article summarizes the discussion of the fundamental photophysical properties of fluorescent tin metal complexes focusing on their recent advances in "biomedical molecular imaging". A debate on the design of tin complexes as cellular imaging agents relating to their chemical, electronic and photophysical properties is enclosed. This paper also discusses the imaging applications of tin complexes in cells, tissues, and organisms via confocal and multiphoton imaging for sensing mechanisms in cellular media, bioimaging, and therapeutic labeling. In addition, it explores and explains the current challenges and prospects associated with these tin complexes as emerging luminescent cellular agents for potential clinical use.