Tribological properties of organotin compound modified UHMWPE

A range of ultra-high molecular weight polyethylene (UHMWPE)/tetraphenyltin (Ph4Sn) nanocomposites were fabricated by hot-pressing. The surface hardness and crystallinity of composites were studied. It revealed that the surface hardness of the composites decreased slightly, and the changing trend of crystallinity was consistent with the hardness. The tribological properties of composites under seawater lubricating conditions were investigated. The experimental results showed that the friction coefficients of the composites almost keep the same but the wear reduced sharply. With the increases of Ph4Sn content, the wear of composites first decreases significantly and then increases, meanwhile the friction coefficient remains basically unchanged. The dominant wear mechanism has changed from adhesive wear to plastic deformation and finally to abrasive wear. The addition of Ph4Sn particles reduces the sensitivity of the Ph4Sn/UHMWPE composites to water and transfers the load to the UHMWPE network, resulting in the wear resistance improved.

Antimetastatic effect of organotin compounds on the model of melanoma B16 in the experiment.

e21564 Background: Melanoma is an extremely malignant tumor. The unfavorable prognosis in the treatment of patients is mainly due to aggressive metastasis of the tumor in various ways: hematogenic, lymphogenic and lymphohematogenic. Metastatic melanoma cells are relatively drug - resistant. Despite some successes in the treatment of melanoma, the search for new antimetastatic substances remains an urgent task of experimental pharmacology and oncology. Organotin compounds were studied by us as promising candidates for antimetastatic agents. Methods: The study was conducted on experimental C57BL/6 mice (n =72, each cohort contained 12 mice) with B16 melanoma (subcutaneous transplantation) to determine the intensity of metastasis in the presence of the cytotoxic organotin compound dimethyltin bis (3,5-di-tert-butyl-4-hydroxyphenylthiolate) [1-3] (Me3). 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). Female mice (8 weeks of age, weighing 21-22 g) were administered intraperitoneal 1% aqueous gelatin solution of organotin Me3 daily for 5 days. The total doses in the first series of the experiment were 150, 250, 375 mg/kg (I, II, III cohorts and IV control group), which allowed us to choose the most effective dose of Me3. After that, in the second series of experiments, the metastasis inhibition index was evaluated in group V (total dose 375 mg/kg) and control group VI. The animals were euthanized on the 18th day after the tumor was inoculated. Results: It was shown that when administered intraperitoneal to mice, Me3 did not inhibit the growth of B16 melanoma in any of the groups. The results showed that the average life expectancy of animals in the experimental group III with the introduction of Me3 at a dose of 375 mg/kg significantly increased and amounted to 30.1±2.5 days, in control mice of group IV-21.8±2.6 days. In the second series of the experiment, after 18 days, the index of metastasis inhibition was almost twice lower (54%) in group V than in the control group (VI). Conclusions: It is concluded that the overall result of this study clearly demonstrates that the organotin compound dimethyltin bis (3,5-di-tert-butyl-4-hydroxyphenylthiolate) (Me3) is an effective antimetastatic agent in transplanted experimental mouse melanoma B16 at a total dose of 375 mg/kg.

Organotin compounds as effective antimetastatic substances in the treatment of epidermoid lung carcinoma Lewis (LLC) in an experiment.

e15054 Background: Lung cancer occupies one of the first places in the structure of oncological diseases in the world. Reducing the life expectancy of patients, as a rule, occurs as a result of metastatic complications, so the search for new antimetastatic agents is an urgent task for experimental pharmacology and oncology. The aim of our study is to assess the severity of metastatic lesion in the Lewis lung epidermoid carcinoma (LLC) model in the presence of an organotin compound. Methods: The study was conducted on experimental C57BL/6 mice (n = 24, each group contained 12 mice) with LLC (subcutaneous transplantation) in the presence of the cytotoxic organotin compound 2,6-bis (1,1-dimethylethyl) - 4 - [(triphenylstannyl)thio]phenol (Me5). 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). Female mice (8 weeks of age, weighing 21-22 g) were intraperitoneally injected with a 1% aqueous gelatin solution of organotin Me5 daily for 5 days. The most effective total dose of Me5 was 250 mg / kg. The animals of the control group received saline solution in similar modes and volumes. In the experimental and control groups, the degree of metastatic lesion was assessed on the 21-day post-grafting period according to the scale proposed by D. Tarin and J. E. Price, which allows us to differentiate the severity of the lesion depending on the number of metastases and their size. The experiment describes three degrees of lesion: LCP-1 (metastases less than 10 pcs. with a diameter not exceeding 1 mm); LCP-2 (metastases from 10 to 30 pieces, some of them larger than 1 mm) and HCP-3 (metastases larger than 30 pieces of different sizes, but no drain). The pathohistological structure was studied by the light-optical method with hematoxylin and eosin staining. Results: When administered intraperitoneal to mice, Me5 did not inhibit the growth of the primary tumor site in the experimental group, but significantly reduced the severity of metastatic lesions in the lungs. In the control group, 75 % of mice with LLC had LCP - 2 (low colonization potential) and in 25% of HCP-3 (high colonization potential) metastatic lesions, in the experimental group only mild lesions were noted in all animals: 58% of mice had LCP – 1, 42% - LCP-2. Conclusions: It is concluded that the overall result of this study clearly demonstrates that the organotin compound 2,6-bis (1,1-dimethylethyl) - 4 - [(triphenylstannyl)thio] phenol (Me5) is an effective antimetastatic agent in the Lewis lung epidermoid carcinoma (LLC) model at a total dose of 250 mg/kg.

Fabrication of a honeycomb-like bimetallic SERS substrate for detection of triphenyltin chloride

Triphenyltin chloride (TPhT), an organotin compound incurs intensive toxicological risk to the environment and humans. A detection method with high sensitivity and stability is therefore desired to better detect TPhT....

Autophagy is Activated In Vivo during Trimethyltin-Induced Apoptotic Neurodegeneration: A Study in the Rat Hippocampus

Trimethyltin (TMT) is an organotin compound known to produce significant and selective neuronal degeneration and reactive astrogliosis in the rodent central nervous system. Autophagy is the main cellular mechanism for degrading and recycling protein aggregates and damaged organelles, which in different stress conditions, such as starvation, generally improves cell survival. Autophagy is documented in several pathologic conditions, including neurodegenerative diseases. This study aimed to investigate the autophagy and apoptosis signaling pathways in hippocampal neurons of TMT-treated (Wistar) rats to explore molecular mechanisms involved in toxicant-induced neuronal injury. The microtubule-associated protein light chain (LC3, autophagosome marker) and sequestosome1 (SQSTM1/p62) (substrate of autophagy-mediated degradation) expressions were examined by Western blotting at different time points after intoxication. The results demonstrate that the LC3 II/I ratio significantly increased at 3 and 5 days, and that p62 levels significantly decreased at 7 and 14 days. Immunofluorescence images of LC3/neuronal nuclear antigen (NeuN) showed numerous strongly positive LC3 neurons throughout the hippocampus at 3 and 5 days. The terminal deoxynucleotidyltransferase dUTP nick end labeling (TUNEL) assay indicated an increase in apoptotic cells starting from 5 days after treatment. In order to clarify apoptotic pathway, immunofluorescence images of apoptosis-inducing factor (AIF)/NeuN did not show nuclear translocation of AIF in neurons. Increased expression of cleaved Caspase-3 was revealed at 5–14 days in all hippocampal regions by Western blotting and immunohistochemistry analyses. These data clearly demonstrate that TMT intoxication induces a marked increase in both autophagy and caspase-dependent apoptosis, and that autophagy occurring just before apoptosis could have a potential role in neuronal loss in this experimental model of neurodegeneration.

Organotin compound DBDCT induces CYP3A suppression through NF-κB-mediated repression of PXR activity

Organotin anticancer agent di-n-butyl-di-(4-chlorobenzohydroxamato)tin(iv) (DBDCT) exerted an inhibitory effect on its major metabolic enzyme cytochrome CYP3A.