Triphenyltin Research Articles

Antitumor pharmacological activity of hybrid organotin compounds on the Lewis epidermoid carcinoma model.

e15004 Background: New antitumor agents based on organic metal derivatives are intensively determined and created by now. Tin compounds are of great interest among them [Milaeva E.R.et al. Novel selective anticancer agents based on Sn and Au complexes. Pure & Applied Chemistry. 2020, 92, 1201-1216]. The results of studies on cell line models allowed us to conclude that cytotoxic effect of organotin compounds is pronounced, so it is advisable to hold their further studies on biological models in vivo [ Dodokhova M.A. et al. Pharmacotherapeutic potential’s evaluation of organotin compounds in vivo Biopharmaceutical journal, 13(3), 30 – 34 (2021); doi: 10.30906/2073-8099-2021-13-3-30-34]. For the specialists of experimental pharmacology and oncology is relevant to rate the antitumor activity of hybrid organotin compounds on experimental malignant tumors. Methods: The study was held on C57Bl/6 mice (females, n = 36, each cohort contained 12 mice) on a Lewis epidermoid carcinoma model (subcutaneous transplantation) [Kit O.I. et al. Influence of chronic neurogenic pain on the dynamics of the no-system functioning during melanoma B16/F10 growth in male mice. Siberian Journal of Oncology, 2021, 20(3), 67–75]. Bis-(3,5-di-tert-butyl-4-hydroxyphenyl)dimethyl tin(Me-3) and (3,5–di–tert–butyl–4–hydroxyphenylthiolate) triphenyl tin (Me-5) were used as chemotherapeutic agents. Groups of animals were formed as follows: I (experimental) - Me-3 at a dose of 75 mg / kg; II (experimental) - Me-5 at a dose of 50 mg / kg; III (control group) - without pharmacological substances. The doses were characterized as the most effective according to the results of a pharmacological activity screening study. The compounds were injected intraperitoneally daily for 5 days. All animals were euthanized since 21 days after the tumor cells transplantation. The antitumor effect was estimated by the percentage of tumor growth inhibition by weight (%). All manipulations were carried out in accordance with the European Convention for the Protection of Vertebrates Used for Experimental and Other Scientific Purposes (ETS 123). Results: After the intraperitoneal injection of chemical substances Me-3 and Me-5, there was revealed an inhibition of growth by weight of Lewis epidermoid carcinoma’s primary node for all experimental groups, 23.7% and 28% respectively. Conclusions: The injection of organotin compounds with different ligand groups allows us to suggest a biocidal activity of the organotin component on the primary tumor node cells.

Reproductive toxicity of environmental levels of triphenyltin to the marine rotifer, Brachionus plicatilis

Triphenyltin (TPT) is a representative organotin often used in marine antifouling coatings, herbicides, and pesticides. However, leaching of TPT into water may be toxic to aquatic life. In this study, environmental concentrations of TPT were used to explore reproductive toxicity of TPT to Brachionus plicatilis, a representative marine rotifer. Toxicity was examined at individual, biochemical, and molecular levels and via phenotypic traits. Rotifers exposed to 10 ng/L TPT group showed increased population size, improved reproductive rate, and a higher weekly growth rate. At 100 ng/L TPT group, the greatest degree of oxidative damage was seen. Exposure to 200 ng/L TPT group shorten generation time, delayed reproduction, and obscured the reproductive peak. Expression of the Vasa gene associated with reproduction was increased after exposure to 10 and 200 ng/L TPT group and decreased at 100 ng/L TPT group. High concentrations of TPT reduced rotifer body length and width and slowed swimming speed. Findings provide a better understanding of the adverse effects of changing TPT concentrations on marine rotifer, by the life cycle parameters, oxidative stress defense mechanisms, expression of a gene related to reproduction, and phenotypic traits. This paper firstly analyzed the reproductive toxicity of environmental levels of organotin compounds to zooplankton, which provided new data support for the comprehensive evaluation of its marine ecological toxicity.

Interaction of Carrier Protein with Potential Metallic Drug Candidate N-Glycoside 'GATPT': Validation by Multi-Spectroscopic and Molecular Docking Approaches.

Lysozyme is often used as a model protein to study interaction with drug molecules and to understand biological processes which help in illuminating the therapeutic effectiveness of the drug. In the present work, in vitro interaction studies of 1-{(2-hydroxyethyl)amino}-2-amino-1,2-dideoxy-d-glucose triphenyl tin (IV) (GATPT) complex with lysozyme were carried out by employing various biophysical methods such as absorption, fluorescence, and circular dichroism (CD) spectroscopies. The experimental results revealed efficient binding affinity of GATPT with lysozyme with intrinsic binding (Kb) and binding constant (K) values in the order of 105 M−1. The number of binding sites and thermodynamic parameters ΔG, ΔH, and ΔS at four different temperatures were also calculated and the interaction of GATPT with lysozyme was found to be enthalpy and entropy driven. The CD spectra revealed alterations in the population of α–helical content within the secondary structure of lysozyme in presence of GATPT complex. The morphological analysis of the complex with lysozyme and lysozyme-DNA condensates was carried out by employing confocal and SEM studies. Furthermore, the molecular docking studies confirmed the interaction of GATPT within the larger hydrophobic pocket of the lysozyme via several non-covalent interactions.

Insights into the Influence of Natural Retinoic Acids on Imposex Induction in Female Marine Gastropods in the Coastal Environment

Conventionally, development of imposex, i.e., superimposition of male sexual characteristics on females, in marine neogastropods has been solely linked to exposure to synthetic organotin compounds, such as triphenyltin (TPT), in the marine environment. Here, our experimental results show that marine cyanobacteria can produce retinoic acids (RAs) and their oxidative metabolites 4-oxo-RAs, and the most commonly distributed RA, i.e., all-trans-RA, can also trigger expression of genes related to imposex in female whelks Reishia clavigera after chronic exposure of 60 days. Both estimated concentrations of TPT and RAs and 4-oxo-RAs in seawater are positively associated with the Vas Deferens Sequence Index (VDSI) in female whelks collected from various sites along the coast of Hong Kong; the concentration of TPT explains 28% of the total variation of VDSI, while the total concentrations of RAs and 4-oxo-RAs contributed to 14% of the variation based on separate regression analyses. Our discoveries have implications on the cause and magnitude of imposex in marine neogastropods, calling for more research in ecotoxicology of natural RAs and 4-oxo-RAs in the marine environment in the future.

The effects of TPT and dietary quercetin on growth, hepatic oxidative damage and apoptosis in zebrafish

The objective of this study was to determine the effects of triphenyltin (TPT) and dietary quercetin on the growth, oxidative stress and apoptosis in zebrafish. A total of 240 fish were divided into 4 groups with three replicates as follows: fish were fed with the basal diet as the control group (D1), only 10 ng/L TPT (D2), 10 ng/L TPT + 100 mg/kg quercetin (D3), and only 100 mg/Kg quercetin as the D4 group. At the end of the study period (56 d), the results showed that the growth performance of the fish that were fed 100 mg/kg quercetin was significantly higher than that of fish that were exposed to 10 ng/L TPT. Quercetin ameliorated oxidative stress, which decreased malondialdehyde (MDA) and nitric oxide (NO) levels and improved antioxidant enzyme activities. The mRNA expressions of the key apoptotic gene and pro-inflammatory cytokines were significantly induced by TPT exposure. However, dietary quercetin prevented a marked increase in the Bax, caspase3 and caspase9 transcript abundances that were induced by TPT. In addition, the quercetin treatments decreased inflammation by regulating the NF-kB signalling pathway. In conclusion, our findings suggested that TPT induced oxidative stress and apoptosis in zebrafish and that the pretreatment with quercetin showed an ameliorative role. Dietary 100 mg/ kg quercetin helps to prevent oxidative damage, apoptosis and inflammation in TPT treated zebrafish.

An ancestral nuclear receptor couple, PPAR-RXR, is exploited by organotins

Environmental chemicals have been reported to greatly disturb the endocrine and metabolic systems of multiple animal species. A recent example involves the exploitation of the nuclear receptor (NR) heterodimeric pair composed by PPAR/RXR (peroxisome proliferator-activated receptor/retinoid X receptor), which shows lipid perturbation in mammalian species. While gene orthologues of both of these receptors have been described outside vertebrates, no functional characterization of PPAR has been carried in protostome lineages. We provide the first functional analysis of PPAR in Patella sp. (Mollusca), using model obesogens such as tributyltin (TBT), triphenyltin (TPT), and proposed natural ligands (fatty acid molecules). To gain further insights, we used site-directed mutagenesis to PPAR and replaced the tyrosine 277 by a cysteine (the human homologous amino acid and TBT anchor residue) and an alanine. Additionally, we explored the alterations in the fatty acid profiles after an exposure to the model obesogen TBT, in vivo. Our results show that TBT and TPT behave as an antagonist of Patella sp. PPAR/RXR and that the tyrosine 277 is important, but not essential in the response to TBT. Overall, these results suggest a relation between the response of the mollusc PPAR-RXR to TBT and the lipid profile alterations reported at environmentally relevant concentrations. Our findings highlight the importance of comparative analysis between protostome and deuterostome lineages to decipher the differential impact of environmental chemicals.

Triphenyltin exposure causes changes in health-associated gut microbiome and metabolites in marine medaka

Triphenyltin (TPT), an organic compound with a wide range of applications, is often detected in water bodies and aquatic animals. However, the mechanism underlying the biological metabolic health problems caused by long-term exposure to environment concentrations of TPT remains unclear. The morphology and gene expression in the gut and liver were investigated; and 16SrRNA gene amplification sequencing and non-targeted LC-MS/MS metabonomics were investigated after marine medaka (Oryzias melastigma) was treated with 1, 10, and 100 ng/L TPT for 21 days. During prolonged exposure to TPT, the adaptation mechanism maximized the energy of absorption, increased the length of intestinal microvilli, reduced the number of rough endoplasmic reticulum in the liver, and caused loss of weight. TPT exposure significantly changed the intestinal microbiome of marine medaka, thereby resulting in a significant decrease in microbial diversity. Following exposure to 100 ng/L TPT, the metabolic profiles were significantly changed and the altered metabolites were mainly concentrated in the lipid metabolic pathway. Finally, based on comprehensive network analysis, the association between the significantly changed bacteria and metabolites contributed further to the prediction of the impact of TPT on the host. This study provides a novel insight into the underlying mechanisms of host metabolic diseases caused by TPT and emphasizes the importance of monitoring pollutants in the environment.

In Vitro Evaluation of Antiproliferative Properties of Novel Organotin(IV) Carboxylate Compounds with Propanoic Acid Derivatives on a Panel of Human Cancer Cell Lines.

The synthesis of novel triphenyltin(IV) compounds, Ph3SnLn (n = 1–3), with oxaprozin (3-(4,5-diphenyloxazol-2-yl)propanoic acid), HL1, and the new propanoic acid derivatives 3-(4,5-bis(4-methoxylphenyl)oxazol-2-yl)propanoic acid, HL2, and 3-(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)propanoic acid, HL3, has been performed. The ligands represent commercial drugs or their derivatives and the tin complexes have been characterized by standard analytical methods. The in vitro antiproliferative activity of both ligands and organotin(IV) compounds has been evaluated on the following tumour cell lines: human prostate cancer (PC-3), human colorectal adenocarcinoma (HT-29), breast cancer (MCF-7), and hepatocellular cancer (HepG2), as well as on normal mouse embryonic fibroblast cells (NIH3T3) with the aid of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-12 diphenyltetrazolium bromide) and CV (crystal violet) assays. Contrary to the inactive ligand precursors, all organotin(IV) carboxylates showed very good activity with IC50 values ranging from 0.100 to 0.758 µM. According to the CV assay (IC50 = 0.218 ± 0.025 µM), complex Ph3SnL1 demonstrated the highest cytotoxicity against the caspase 3 deficient MCF-7 cell line. Inductively coupled plasma mass spectrometry (ICP-MS) analysis indicated a two-fold lower concentration of tin in MCF-7 cells in comparison to platinum. To investigate the mechanism of action of the compound Ph3SnL1 on MCF-7 cells, morphological, autophagy and cell cycle analysis, as well as the activation of caspase and ROS/RNS and NO production, has been performed. Results suggest that Ph3SnL1 induces caspase-independent apoptosis in MCF-7 cells.

Transcriptomics reveal triphenyltin-induced molecular toxicity in the marine mussel Perna viridis

Triphenyltin (TPT) is widely used as an active ingredient in antifouling paints and fungicides, and continuous release of this highly toxic endocrine disruptor has caused serious pollution to coastal marine ecosystems and organisms worldwide. Using bioassays and transcriptome sequencing, this study comprehensively investigated the molecular toxicity of TPT chloride (TPTCl) to the marine mussel Perna viridis which is a commercially important species and a common biomonitor for marine pollution in Southeast Asia. Our results indicated that TPTCl was highly toxic to adult P. viridis, with a 96-h LC10 and a 96-h EC10 at 18.7 μg/L and 2.7 μg/L, respectively. A 21-day chronic exposure to 2.7 μg/L TPTCl revealed a strong bioaccumulation of TPT in gills (up to 36.48 μg/g dry weight) and hepatopancreas (71.19 μg/g dry weight) of P. viridis. Transcriptome analysis indicated a time course dependent gene expression pattern in both gills and hepatopancreas. Higher numbers of differentially expressed genes were detected at Day 21 (gills: 1686 genes; hepatopancreas: 1450 genes) and at Day 28 (gills: 628 genes; hepatopancreas: 238 genes) when compared with that at Day 7 (gills: 104 genes, hepatopancreas: 112 genes). Exposure to TPT strongly impaired the endocrine system through targeting on nuclear receptors and putative steroid metabolic genes. Moreover, TPT widely disrupted cellular functions, including lipid metabolism, xenobiotic detoxification, immune response and endoplasmic-reticulum-associated degradation expression, which might have caused the bioaccumulation of TPT in the tissues and aggregation of peptides and proteins in cells that further activated the apoptosis process in P. viridis. Overall, this study has advanced our understanding on both ecotoxicity and molecular toxic mechanisms of TPT to marine mussels, and contributed empirical toxicity data for risk assessment and management of TPT contamination.

Assessing the Association of Mitochondrial Function and Inflammasome Activation in Murine Macrophages Exposed to Select Mitotoxic Tri-Organotin Compounds.

Background:Mitochondrial function is implicated as a target of environmental toxicants and found in disease or injury models, contributing to acute and chronic inflammation. One mechanism by which mitochondrial damage can propagate inflammation is via activation of the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family, pyrin domain-containing receptor (NLRP)3 inflammasome, a protein complex that processes mature interleukin . plays an important role in the innate immune response and dysregulation is associated with autoinflammatory disorders.Objective:The objective was to evaluate whether mitochondrial toxicants recruit inflammasome activation and processing.Method:Murine macrophages (RAW 264.7) exposed to tri-organotins (triethyltin bromide (TETBr), trimethyltin hydroxide (TMTOH), triphenyltin hydroxide (TPTOH), bis(tributyltin)oxide) [Bis(TBT)Ox] were examined for pro-inflammatory cytokine induction. TMTOH and TETBr were examined in RAW 264.7 and bone marrow-derived macrophages for mitochondrial bioenergetics, reactive oxygen species (ROS) production, and inflammasome activation via visualization of aggregate formation, caspase-1 flow cytometry, enzyme-linked immunosorbent assay and Western blots, and microRNA (miRNA) and mRNA arrays.Results:TETBr and TMTOH induced inflammasome aggregate formation and release in lipopolysaccharide (LPS)-primed macrophages. Mitochondrial bioenergetics and mitochondrial ROS were suppressed. Il1a and Il1b induction with LPS or challenge was diminished. Differential miRNA and mRNA profiles were observed. Lower miR-151-3p targeted cyclic adenosine monophosphate (cAMP)-mediated and AMP-activated protein kinase signaling pathways; higher miR-6909-5p, miR-7044-5p, and miR-7686-5p targeted Wnt beta-catenin signaling, retinoic acid receptor activation, apoptosis, signal transducer and activator of transcription 3, IL-22, IL-12, and IL-10 signaling. Functional enrichment analysis identified apoptosis and cell survival canonical pathways.Conclusion:Select mitotoxic tri-organotins disrupted murine macrophage transcriptional response to LPS, yet triggered inflammasome activation. The differential response pattern suggested unique functional changes in the inflammatory response that may translate to suppressed host defense or prolong inflammation. We posit a framework to examine immune cell effects of environmental mitotoxic compounds for adverse health outcomes. https://doi.org/10.1289/EHP8314

Synthesis and cytotoxic activity of organotin(IV) diallyldithiocarbamate compounds as anticancer agent towards colon adenocarcinoma cells (HT-29).

ContextDiphenyltin(IV) diallyldithiocarbamate compound (Compound 1) and triphenyltin(IV) diallyldithiocarbamate compound (Compound 2) are two newly synthesised compounds of organotin(IV) with diallyldithiocarbamate ligands.ObjectiveTo assess the cytotoxic effects of two synthesised compounds against HT-29 human colon adenocarcinoma cells and human CCD-18Co normal colon cells.Materials and methodsTwo successfully synthesised compounds were characterised using elemental (carbon, hydrogen, nitrogen, and sulphur) analysis, Fourier-Transform Infrared (FTIR), and 1H, 13C 119Sn Nucleus Magnetic Resonance (NMR) spectroscopies. The single-crystal structure of both compounds was determined by X-ray single-crystal analysis. The cytotoxicity of the compounds was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazholium bromide (MTT) assay upon 24 h of treatment. While the mode of cell death was determined based on the externalisation of phosphatidylserine using a flow cytometer.ResultsThe elemental analysis data of the two compounds showed an agreement with the suggested formula of (C6H5)2Sn[S2CN(C3H5)2]2 for Compound 1 and (C6H5)3Sn[S2CN(C3H5)2] for Compound 2. The two major peaks of infrared absorbance, i.e., ν(C = N) and ν(C = S) were detected at the range of 1475–1479 cm−1 and 972–977 cm−1, respectively. The chemical shift of carbon in NCS2 group for Compound 1 and 2 were found at 200.82 and 197.79 ppm. The crystal structure of Compound 1 showed that it is six coordinated and crystallised in monoclinic, P21/c space group. While the crystal structure of Compound 2 is five coordinated and crystallised in monoclinic, P21/c space group. The cytotoxicity (IC50) of the two compounds against HT-29 cell were 2.36 μM and 0.39 μM. Meanwhile, the percentage of cell death modes between 60% and 75% for compound 1 and compound 2 were mainly due to apoptosis, suggesting that both compounds induced growth arrest.ConclusionOur study concluded that the synthesised compounds showed potent cytotoxicity towards HT-29 cell, with the triphenyltin(IV) compound showing the highest effect compared to diphenyltin(IV).

Insights into the Regulation on Proliferation and Differentiation of Stem Leydig Cells.

Male hypogonadism is a clinical syndrome caused by testosterone deficiency. Hypogonadism can be caused by testicular disease (primary hypogonadism) or hypothalamic-pituitary dysfunction (secondary hypogonadism). The present strategy for treating hypogonadism is the administration of exogenous testosterone. But exogenous testosterone is reported to have negative side effects including adverse cardiovascular events and disruption of physiological spermatogenesis probably due to its inability to mimic the physiological circadian rhythm of testosterone secretion in vivo. In recent years, a growing number of articles demonstrated that stem Leydig cells (SLCs) can not only differentiate into functional Leydig cells (LCs) in vivo to replace chemically disrupted LCs, but also secrete testosterone in a physiological pattern. The proliferation and differentiation of SLCs are regulated by various factors. However, the mechanisms involved in regulating the development of SLCs remain to be summarized. Factors involved in the regulation of SLCs can be divided into environmental pollutants, growth factors, cytokine and hormones. Environmental pollutants such as Perfluorooctanoic acid (PFOA) and Triphenyltin (TPT) could suppress SLCs proliferation or differentiation. Growth factors including FGF1, FGF16, NGF and activin A are essential for the maintenance of SLCs self-renewal and differentiation. Interleukin 6 family could inhibit differentiation of SLCs. Among hormones, dexamethasone suppresses SLCs differentiation, while aldosterone suppresses their proliferation. The present review focuses on new progress about factors regulating SLC's proliferation and differentiation which will undoubtedly deepen our insights into SLCs and help make better clinical use of them. Different factors affect on the proliferation and differentiation of stem Leydig cells. Firstly, each rat was intraperitoneally injected EDS so as to deplete Leydig cells from the adult testis. Secondly, the CD51+ or CD90+ cells from the testis of rats are SLCs, and the p75+ cells from human adult testes are human SLCs. These SLCs in the testis start to proliferate and some of them differentiate into LCs. Thirdly, during the SLCs regeneration period, researchers could explore different function of those factors (pollutants, growth factors, cytokines and hormones) towards SLCs.

Potent inhibition of tributyltin (TBT) and triphenyltin (TPT) against multiple UDP-glucuronosyltransferases (UGT): A new potential mechanism underlying endocrine disrupting actions

Organotin compounds (OTs) act as potent endocrine disruptors that are often found in polluted food and water. UDP-glucuronosyltransferases (UGTs) are responsible for termination of multiple endogenous hormones. This study was conducted to investigate the inhibitory effects of two tri-submitted OTs tributyltin (TBT) and triphenyltin (TPT), against activities of UGTs. It is revealed that TBT and TPT act as two potent inhibitors for multiple UGTs. UGT1A8 and -2B15 were coinhibited by the two OTs. UGT1A1 and -1A10 were inhibited by TPT, whereas UGT 2B4 and -2B7 were inhibited by TBT. Kinetic analyses further indicated that TBT and TPT are two competitive nanomolar inhibitors of UGT2B15, with Ki values of 0.45 and 0.46 μM, respectively. Ki values for the other UGTs are determined to be a few micromolars. In addition, the two OTs displayed effective inhibition against UGT2B15 in catalyzing dihydrotestosterone glucuronidation, with IC50 values both in nano-molar range. TPT can additionally inhibit activities of UGT1A1 and -1A10 in estradiol-3-O-glucuronidation, with IC50 values of a few micro-molars. These results indicated that the two OTs can extensively interfere with glucuronidation of endogenous hormones, which may act as a new potential mechanism resulting in endocrine disrupting actions.

Distribution of antifouling biocides in a coastal area of Tanabe Bay, Japan

AbstractTributyltin (TBT) and triphenyltin (TPT) concentrations in water samples from Tanabe Bay were found to range from 4–28 ng l−1 and 3–7 ng l−1, respectively. In fishing ports, the concentrations of TBT in surface water were similar to those in bottom water. However, in aquafarming areas with poor flushing, the concentrations of TBT in bottom water were higher than those in surface water. This suggested that the TBT in water samples is re-eluted from sediment. No difference in the concentration of TPT was observed between the surface and bottom waters. The concentrations of TBT and TPT in sediment samples ranged from 3–23 μg kg−1 dry weight and 2–37 μg kg−1 dry weight. TBT and TPT concentrations ranged from 3.1–100 μg kg−1 and 3.1–7.2 μg kg−1 in oysters and gastropods, and from 1.1–4.9 μg kg−1 and ＜0.2–3.9 μg kg−1 in fish, respectively. Organotin concentrations in biota were lower than the tolerable average residue levels (TARLs). Alternative biocides – i.e. diuron, chlorothalonil, dichlofluanid, irgarol 1051 and Sea-Nine 211 – were also detected in surface water, and chlorothalonil and irgarol 1051 were detected in sediment. The concentrations of these compounds in surface water and sediment were lower than those reported previously. Dichlofluanid, chlorotharonil and irgarol 1051 were also found at low levels in oysters and gastropods, and at ranges of 325–339 μg kg−1, 268–291 μg kg−1 and 43–49 μg kg−1, respectively, in fish; the concentrations in fish were close to the TARL levels.

Modulatory effect of fructooligosaccharide against triphenyltin-induced oxidative stress and immune suppression in goldfish (Carassius auratus)

Triphenyltin (TPT) is a widely used pesticide that is highly toxic to a variety of organisms, including humans, and is a potential contributor to environmental pollution. The present study was conducted to evaluate the oxidative stress and immunotoxicity induced by TPT in goldfish (Carassius auratus) and the protective effects of fructooligosaccharide (FOS). Goldfish (mean weight of 13.3 ± 0.2 g) were randomly divided into six groups with three replicates: (G1) the control group, (G2) the 10 ng/L TPT group, (G3) the 0.4% FOS group, (G4) the 10 ng/L TPT + 0.4% FOS group, (G5) the 0.8% FOS group, and (G6) the 10 ng/L TPT + 0.8% FOS group. The results showed that 10 ng/L TPT induced oxidative stress and significantly decreased the activities of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), in the liver and the gene expression of SOD, GPx, metallothionein (MT), and peroxiredoxin-4 (Prdx-4). The concentration of malondialdehyde (MDA) and the gene expression of cytochrome P450 (CYP) and glutathione S-transferase (GST) in the liver were significantly increased in the TPT-treated group. Exposure to 10 ng/L TPT in water induced immune suppression and significantly decreased the activities of immune enzymes, such as lysozyme, myeloperoxidase (MPO), alternative complement (ACH50), acid phosphatase (ACP) and alkaline phosphatase (AKP), in the serum. TPT could stimulate the fish to generate large amounts of proinflammatory cytokines, including increased tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and nitric oxide (NO) levels and TNF-α, IL-6, IL-1β, and NF-κB mRNA expression. However, TPT-induced toxicity was significantly ameliorated in the groups treated with FOS, and FOS partly prevented alterations in the activities of antioxidant enzymes and the expression of antioxidant- and ROS scavenger-related genes. In addition, TPT-induced immune toxicity was significantly ameliorated in the groups treated with FOS. FOS markedly suppressed TNF-α, IL-6, IL-1β, and NO production and TNF-α, IL-6, and IL-1β mRNA expression in the TPT-treated groups. The study indicated that TPT-induced oxidative stress may play a critical role in inhibiting immunity. However, FOS administration attenuates TPT-induced oxidative stress and immune suppression in goldfish.

Synthesis and crystal structure of the one-dimensional chain triphenyltin compound bridged by 5-chloro-6-hydroxynicotinic acid

Reaction of 5-chloro-6-hydroxynicotinic acid with Ph3SnCl and sodium ethoxide in 1:1:1 stoichiometry yielded triphenyltin compound. This compound has been characterized by single crystal X-ray diffraction, elemental analysis, IR and 1H NMR spectroscopy. In the molecular structure of the title compound, the tin atoms are five-coordinated in a distorted trigonal bipyramidal geometry. The resulting structure is 1D linear polymer through an interaction between the O atoms of phenolic hydroxide and tin atoms of an adjacent molcule. The compound exhibit high antitumor activity.

Determination of Tributyltin and Triphenyltin in Fish and Shellfish Using Accelerated Solvent Extraction and Liquid Chromatography with Tandem Mass Spectrometry

A determination method for tributyltin (TBT) and triphenyltin (TPT) in fish and shellfish using an accelerated solvent extractor (ASE) and LC-MS/MS was developed. The chromatographic separation was conducted on a Poroshell 120 EC-C18 column using an isocratic mobile phase of 0.1% formic acid in 70% methanol. Sample preparation was performed using ASE at 125℃ with n-hexane and a cleanup using a Florisil cartridge. Internal calibration curves using deuterium-labeled TBT and TPT were employed for quantification. For both TBT and TPT, the calibration curves were linear in the range of 0.2-250 ng/mL, and the method quantification limits were 0.8 ng/g for both TBT and TPT. A National Institute for Environmental Studies certified reference material, No. 15 (adductor muscle of scallop), was analyzed to assess the performance of the developed method. The trueness, relative standard deviations of repeatability, and within laboratory reproducibility of this method, evaluated using a recovery test with four spiked fish species and one shellfish, ranged from 89.3 to 105.3%, 1.0 to 4.5%, and 1.3 to 7.6%, respectively.

Speciation and quantification of organotin compounds in Lagos harbour, Nigeria

ABSTRACT The application of organotin-based antifouling compounds in the harbour during repairing and painting of ships in Nigeria harbour is a common practice in the maintenance wing of the dockyard. These antifouling chemicals are extremely toxic to aquatic life. As a result of dearth of data on the levels of organotin compounds in the West African coast including Lagos harbour, a study was undertaken to profile organotin compounds, in Lagos Dockyard harbour, Nigeria. The sediment and water samples were collected for two years (2016–2018) covering both the dry and wet seasons. A cold extraction technique by ultrasonication was used for sediments collected and a liquid-liquid separation technique was applied to water samples and later cleaned up by the use of silica gel-based packed column. The six organotin compounds considered in this work are Monobutyltin (MBT), Dibutyltin (DBT), Tributyltin (TBT), Monophenyltin (MPhT), Diphenyltin (DPhT), Triphenyltin (TPhT) were analysed by using an optimised high-performance liquid chromatography (HPLC). The result of the analysis on the sediment showed that the concentration of the organotin compounds (OTCs) ranges from 0.008 ± 0.00 to 272.710 ± 100.2 (ng/g) in MBT, 0.001 ± 0.00 to 69.780 ± 42.01 (ng/g) in DBT, 0.002 ± 0.00 to 7.110 ± 0.45 (ng/g) in TBT, 0.046 ± 0.01 to 76.210 ± 4.00 (ng/g) in MPhT, 0.070 ± 0.01 to 11.520 ± 0.62 (ng/g) in DPhT and 0.006 ± 0.00 to 2.330 ± 0.04 (ng/g) in TPhT. Higher values of OTCs were recorded during the wet season than the dry season and this was attributed to the dredging of harbour and remobilisation of organotin compounds from sediments into the water compartment. Principal Component Analysis (PCAs), Cluster Analysis (CA) and correlation analysis provided evidence for the interaction among these contaminants and possible sources of the contaminants. More so, the study showed that the degradation of these organotin compounds into their metabolites was governed by the influence of specific microorganisms. Therefore, regular monitoring of harbour was recommended for public safety.

Influence of triphenyltin on morphologic abnormalities and the thyroid hormone system in early-stage zebrafish (Danio rerio)

In the present study, we assessed the negative effects of triphenyltin (TPT) on zebrafish (Danio rerio) by exposing embryos and early-stage larvae to various concentrations of TPT from 2 h after fertilization (haf) until 30 days after hatching (dah). Whether test groups were fed or fasted during ecotoxicity studies using fish models has varied historically, and whether this experimental condition influences test results is unknown. Here, we confirmed that the lethal concentration of TPT to embryo and early-stage larvae (i.e., 3 dah or younger) showed in fed (lowest observed effect concentration (LOEC); 6.34 μg/L) and fasted (LOEC; 6.84 μg/L) groups. In addition, 84% and 100% of the larvae in the 2.95 and 6.64 μg/L exposure groups, respectively, had uninflated swim bladders; all affected larvae died within 9 dah. This finding suggests that morphologic abnormalities in early larval zebrafish are useful as endpoints for predicting the lethality of chemical substances after hatching. We then assessed the expression of several genes in the thyroid hormone pathway, which regulates swim bladder development in many fish species, including zebrafish. Larvae exposed to 6.64 μg/L TPT showed significant increases in the mRNA expression levels of thyroid hormone receptor α (trα) and trβ but not of thyroid stimulating hormone β subunit. These findings suggest that TPT disrupts the thyroid system in zebrafish.

Triorganotin(IV) derivatives with semirigid heteroditopic hydroxo‐carboxylato ligands: Synthesis, characterization, and cytotoxic properties

Three organic hydroxy‐carboxylic acids separated by a semirigid aromatic diaza scaffold and carrying alkyl groups of different steric hindrance (H′HL1, cyclopropyl; H′HL2, cyclohexyl; H′HL3, adamantyl) were employed as pro‐ligands. Their reaction with suitable triorganotin precursors leads to 10 complexes of compositions: [Me3Sn(HL1)]n·0.5nC6H5CH3 1, [Et3Sn(HL1)]n 2, [nBu3Sn(HL1)]n 3, [Ph3Sn(HL1)]n 4, [Me3Sn(HL2)]2·2CH2Cl2 5, [Et3Sn(HL2)]2 6, {[nBu3Sn(HL2)][nBu3Sn(HL2)(H2O)]} 7, [Ph3Sn(HL2)]n·nC2H5OH 8, [nBu3Sn(HL3)]n 9, and [Ph3Sn(HL3)]n 10. The solid‐state structures of 1–10 were deduced from single‐crystal X‐ray diffraction studies along with two of the pro‐ligands: H′HL1 and H′HL2. In the solid state, four different extended structure types were observed. In compounds 1–3 with aliphatic substituents at the tin atoms and a small substituent at the ligand backbone (cyclopropyl), 1D coordination polymers based on carboxylate bridging were observed, whereas compounds 4 and 8–10 with large substituents attached to the metal and the ligand (cyclohexyl and adamantyl) were 1D coordination polymers based on heteroditopic binding of the ligands. Albeit having essentially the same ligand conformation, the compounds having smaller substituents at the tin atoms (5, R = Me; 6, R = Et) comprise 24‐membered macrocyclic ring structures. In 7, water molecules are coordinated to half the tin atoms, giving dinuclear fragments {[HL2][nBu3Sn][HL2][nBu3Sn(H2O)]}, which are linked through OwH···Osal hydrogen bonds into 1D hydrogen‐bonded tapes. In solution, the tin atoms in 1–10 are coordinated to a single monoanionic [HL1–3]− ligand molecule utilizing anisobidentate coordination with the carboxylate group, as revealed from 119Sn nuclear magnetic resonance spectral results. The antiproliferative activity of the tri‐n‐butyl and triphenyltin compounds 3, 4, and 7–10 was evaluated against the cervical cancer cells (HeLa) and normal kidney cells (HEK) using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. Of these, the adamantyl‐substituted tin complexes 9 and 10 present increased activity with IC50 values of 0.51 ± 0.01 and 0.41 ± 0.03 (μM) and good selectivity. The cell death mechanism was identified as apoptosis based on dual staining with fluorescent dyes (Hoechst 33342/propidium iodide and acridine orange/ethidium bromide) and might be related to reactive oxygen species.