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

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21564-e21564
Author(s):  
Margarita Avdeevna Dodokhova ◽  
Inga Movlievna Kotieva ◽  
Dmitriy Borisovich Shpakovsky ◽  
Andrej Vladimirovich Safronenko ◽  
Ekaterina Fedorovna Komarova ◽  
...  

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.

2020 ◽  
Vol 8 (02) ◽  
pp. 55-59
Author(s):  
Reetu Arora ◽  
Yogesh Kumar ◽  
Neetu Jindal ◽  
Renu Aggarwal ◽  
Kavneet Takhar

Abstract Introduction The aim of obturation in the root canal is to completely seal the canal space to eliminate all the portals of entry and exit between root canal and periodontal space. Various techniques have been developed to achieve a hermetic seal. Materials and Methods As many as 150 extracted human maxillary central incisors were taken for the study. Biomechanical preparation was done up to F5 protaper file. According to different obturation techniques, samples were divided into six groups, keeping 30 samples in experimental and 15 samples in control groups. Group I–Lateral Condensation, Group II–Thermafil, Group III–Beefill, Group IV–GuttaFlow, Group V–Positive Control group, Group VI–Negative Control group. After obturation, the samples were immersed in 2% Rhodamine-B dye for 24 hours. Each sample was longitudinally sectioned to examine under confocal laser scanning microscope. Statistical Analysis The results were evaluated with ANOVA and posthoc Tukey honest significant difference (HSD) comparison test. Results The mean values of dye penetration of different groups were Group I (Lateral Condensation) 1.51 ± 0.451, Group II (Thermafil) 0.918 ± 0.399, Group III (Beefill) 1.30 ± 0.559. Group IV (GuttaFlow) 0.655 ± 0.396, Group V (Positive Control group) 1.96 ±0.046, Group VI (Negative Control group) 0 ± 0. The lowest mean value of apical microleakage was found in GuttaFlow amongst all experimental groups. Conclusion It can be concluded that the GuttaFlow obturating material exhibited better apical sealing ability with canal walls.


2012 ◽  
Vol 27 (2) ◽  
pp. 185-192 ◽  
Author(s):  
Conceição Aparecida Dornelas ◽  
Francisco Vagnaldo Fechine-Jamacaru ◽  
Irineu Lima Albuquerque ◽  
Hemerson Iury Ferreira Magalhães ◽  
Adjair Jairo Silva de Souza ◽  
...  

PURPOSE: To determine the effects of green propolis extracted in L-lysine (WSDP) and of L- lysine for 40 weeks on induced rat bladder carcinogenesis. METHODS: The animals (groups I, II, III, IV, V and VI) received BBN during 14 weeks. Group I was treated with propolis 30 days prior received BBN, and then these animals were treated daily with propolis; Groups II and III was treated with subcutaneous and oral propolis (respectively) concurrently with BBN. The animals of Group IV were treated L-lysine; Group V received water subcutaneous; and Group VI received only to BBN. Among the animals not submitted to carcinogenesis induction, Group VII received propolis, Group VIII received L-lysine and Group IX received water. RESULTS: The carcinoma incidence in Group I was lower than that of control (Group VI). The carcinoma multiplicity in Group IV was greater than in Group VI. All animals treated with L-lysine developed carcinomas, and they were also more invasive in Group IV than in controls. On the other hand, Group VIII showed no bladder lesions. CONCLUSION: The WSDP is chemopreventive against rat bladder carcinogenesis, if administered 30 days prior to BBN , and that L-lysine causes promotion of bladder carcinogenesis.


2003 ◽  
Vol 1 (2) ◽  
pp. 50-57 ◽  
Author(s):  
HESTI PUSPITASARI ◽  
SHANTI LISTYAWATI ◽  
TETRI WIDIYANI

The objectives of the research were to find out the effect of giving sedges root extract orally on the number of writhing after chemical pain induction and time reaction after thermal pain induction of mice and also to find out the extract dosage which had an influence on decreasing number of writhing after chemical pain induction and length of reaction time after thermal pain induction of mice. The Complete Random Design (CRD) with 6 treatment groups and each treatment used 5 repetitions were used in this study. The groups were: Group I , control group, treated with sedges root extract of 0 mg/ 20 g BW , 0,5 ml; Group II treated with sedges root extract of 1 mg/ 20 g BW, 0,5 ml; Group III treated with sedges root extract of 3 mg/ 20 g BW, 0,5 ml; Group IV treated with sedges root extract of 5 mg/ 20 g BW, 0,5 ml; Group V treated with sedges root extract of 7 mg/ 20 g BW, 0,5 ml; Group VI treated with asetosal 200 mg/ kg BW , 0,5 ml/ 20 g BW and for the activity test, the sedges root extract was suspended in CMC 1%. Induction of chemical pain was done according to Witkin et al. (1965) in Pudjiastuti et al. (2000), in which 0,1 ml 3% of Acetic Acid/ 20 g BB was injected intraperitoneally 30 minutes after giving oral-material test. The mouse gave a respond in the way of writhing. Thermal pain induction was done by placing the mouse on hot plate with constant temperature of 55oC. The mouse gave a respond in the way of lick its back foot or even jumping. The data collected was analyzed using one direction ANOVA model and it was continued with LSD test in order to find out the difference every treatment group. The result of the analysis showed that the sedges root extract dosage of 7 mg/ 20 g BB decreased the number of writhing after chemical pain induction and length of mouse time reaction after thermal pain induction, so that sedges root extract dosage 7 mg/ 20 g BB had an analgetic function.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15054-e15054
Author(s):  
Margarita Avdeevna Dodokhova ◽  
Inga Movlievna Kotieva ◽  
Andrej Vladimirovich Safronenko ◽  
Dmitriy Borisovich Shpakovsky ◽  
Elena Rudolfovna Milaeva ◽  
...  

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.


Author(s):  
Suganya Vasudevan ◽  
Anuradha Venkataraman

Cancer is a disease in which a group of abnormal cells grow uncontrollably by disregarding the normal rules of cell division. Across several cancers, Hepatocellular carcinoma (HCC) is one of the most aggressive cancers in worldwide. It is held responsible for up to 1 million deaths globally per annum. HCC is an inflammation-related cancer, as a chronic inflammatory state is necessary for cancer appearance. In this study, the drug astaxanthin and encapsulated astaxanthin was tested against HCC. Mice were divided into 7 groups; Group I: control, Group II: DEN induced, Group III: DEN + 50 mg/kg astaxanthin, Group IV: DEN + 100 mg/kg astaxanthin, Group V: DEN + 50 mg/kg encapsulated astaxanthin, Group VI: DEN + 100 mg/kg encapsulated astaxanthin, Group VII: DEN + 10 mg/kg sorafenib. Regular diet was given. Body weight, Food intake, water intake was noted. Other biochemical parameters such as ALP, AST, Albumin, proteins and TNF-α was determined. Finally, the liver was removed from each mice of different group by sacrificing them and histopathology was done. In vivo evaluation in mice models showed significant antitumor activities by both encapsulated and non-encapsulated astaxanthin at 100 mg/kg as compared with the control, DEN induced group and positive drug sorafenib. This research suggested that encapsulated astaxanthin can also be used as chemotherapeutic agent for the treatment of Hepatocellular carcinoma (HCC).


Author(s):  
Waleed K. Ghanim ◽  
Nada N. Al-Shawi

Cyclophosphamide is chemotherapeutic agent that utilized for the treatment of different malignancies; however its’ used associated with numerous adverse effects. Vitamin B2 and vitamin B12 suggested having myeloprotective effect. This work is designed to investigate the myeloprotective effect of both vitamins against cyclophosphamide induced myelosuppression. One hundred adult rats of both sexes were used in this study. The animals were randomly enrolled into ten groups of 10 rats each. Group I: Control group. Group II: Cyclophosphamide-treated. Group III and Group IV Orally-administered vitamin B2 (10, and 40 mg/kg/day), respectively alone for 7 days. Group V: Orally-administered vitamin B12 (0.1 mg/kg/day) alone for 7 days. Group VI and Group VII: Orally-administered vitamin B2 (10, and 40 mg/kg/day), respectively for 7 days and a single IP injection of cyclophosphamide (150 mg/kg) at day 7.Group VIII: Orally-administered vitamin B12 (0.1 mg/kg/day) for 7 days and a single IP injection of cyclophosphamide (150 mg/kg) at day 7. Group IX: Orally-administered a combination of vitamin B2 (10 mg/kg/day) and vitamin B12 (0.1 mg/kg/day) for 7 days and a single IP injection of cyclophosphamide (150 mg/kg) at day 7. Group X: orally-administered a combination of vitamin B2 (40 mg/kg/day) and vitamin B12 (0.1 mg/kg/day) for 7 days and a single IP injection of cyclophosphamide (150 mg/kg) at day 7. On day eight, animals were sacrificed and blood collected for CBCs and femur bone were extracted for bone marrow histological examination. Vitamin B2 and vitamin B12 significantly (P<0.05) increase CBCs; and the combination of vitamins produce -a significant (P<0.05) increase in CBCs compared to corresponding counts in other Groups, and -improve histopathological changes compared to Group II rats. In conclusion both vitamins may have myeloprotective effects against cyclophosphamide-induced myelosuppression.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Nilay Taş ◽  
Özgür Yağan ◽  
Tevfik Noyan ◽  
Sema Nur Ayyıldız ◽  
Y. Burcu Üstün ◽  
...  

Background. Sugammadex is a new reversal agent that has entered use recently. It is known that with sugammadex some changes in coagulation parameters occur without documented clinical results. Aim of the Work. The objective of this study was to identify effects of sugammadex on liver functions, coagulation, and fibrinolytic systems. Methods. Thirty-six rats were randomized into six groups: Group I, control; Group II, rocuronium group; Group III, sugammadex administered in 16 mg kg−1 dose; Group IV, sugammadex administered in 96 mg kg−1 dose; Group V, rocuronium and sugammadex administered in 16 mg kg−1 dose; and Group VI, rocuronium and sugammadex administered in 96 mg kg−1 dose. After 120 minutes, blood samples were obtained for prothrombin time, activated partial thromboplastin time, D-dimer, fibrinogen, aspartate aminotransferase, alanine aminotransferase, albumin, platelet, and mean platelet volume analyses. Results. Compared to the control group, in all groups measured parameters did not show any effect from a statistical viewpoint either due to the administered drugs alone or due to interaction effects. Conclusion. The conclusion was reached that administration of sugammadex in rats did not have any significant effect on the fibrinolytic system, coagulation parameters, and liver function.


Author(s):  
K. S. Adedapo ◽  
S. Adepoju ◽  
T. O. Olusanya

The interplay of hyperlipidemia and oxidative stress in atherosclerosis has been fairly established by previous studies. There remains however, paucity of data in this environment on the direct effects of antioxidants on atherosclerosis. This study therefore aimed at determining the protective effects of EDTA, vitamin C and Vitamin E on atherosclerosis in diet induced heperlipidemic wister rats. Thirty Wister rats were investigated in this study. The rats were randomly divided into five groups (n=6). The control group was fed with growers mash and water only while group II-V were induced with hyperlipidemic diet for ten weeks. In addition to the hyperlipidemic diet; group III received 1 g/kg body weight of EDTA, group IV received 1 g/kg body weight of vitamin C, group V received 1 g/kg body weight of vitamin E, and group VI received EDTA, vitamin C and E. The group’s treatments were orally for two weeks. C-reactive protein, Total cholesterol (TC), Triglyceride (TG), HDL-cholesterol, LDL-cholesterol, Total calcium and Total antioxidant status were analyzed using standard methods after the treatments. The study showed significant effect in the use of EDTA, Vitamin C and Vitamin E in the treatment of atherosclerosis in rats which could be due to their antioxidant and anti-hyperlipidemic properties. Therefore the combinations EDTA, vitamin C and vitamin E appear greatly protective against atherosclerosis.


Author(s):  
M. A. Dodokhova ◽  
I. M. Kotieva ◽  
А. V. Safronenko ◽  
V. G. Trepel ◽  
M. S. Alkhuseyn–Kulyaginova ◽  
...  

Introduction. The aim of the study was to evaluate the effect of hybrid organotin compounds bis(3,5–di– tert–butyl–4–hydroxyphenylthiolate) dimethylol (Me3) and ((3,5–di–tert–butyl–4–hydroxyphenylthiolate) triphenylolol (Me5) on the level of markers of oxidative stress and apoptotic processes in the mitochondria during acute and subchronic intragastric administration to Wistar rats (females) in the maximum tolerated dose. Materials and methods. The objects of study were hybrid organotin compounds, the administration was carried out at the maximum tolerated dose of 2000 mg/kg (Me3) and 750 mg/kg (Me5) with a single and multiple intragastric administration. The study was conducted on 60 Wistar rats (females) weighing 190-210g. The concentration of cytochrome C (ng / g protein), caspase-9(ng / g protein), 8-hydroxy-2' — deoxyguanosine (8-OHdG) (ng/g protein), malondialdehyde (MDA) (nM / g protein)was determined in mitochondrial liver samples using test systems by enzyme immunoassay; by the biochemical method-the amount of protein (mg / ml) — by the biuretic method. Results. Me3 in both series of the experiment showed itself as a more pronounced antioxidant than Me5, which did not show its antioxidant properties. In group I animals, there were no statistically significant differences in the level of MDA and Cit C in relation to the control group, no mitDNA damage was detected, but K9 activity increased by 17%. With the introduction of Me5, the value of the MDA indicator increased by 55.5%, 8 — OHdG by 12.4% and Cit C by 66.2%. In group IV, the amount of MDA as the final product of lipid peroxidation (POL) increased by 13.6%, in group V by 22.5%. With the introduction of Me3, the level of Cit C was reduced by 23.5%, with the introduction of Me5, on the contrary, it was slightly increased. K9 activity was reduced in both experimental groups, by 9.6% and 17.3%, respectively. Discussion. Hybrid OOS containing a fragment of 2,6-di-tert-butylphenol have a dual structure. The tin-containing component is prooxidant, and the radical of the spatially hindered phenol, on the contrary, is antioxidant. It is the different ratio of the described fragments in the molecules of the substances under study, in our opinion, that led to the appearance of different degrees of influence on the metabolism of mitochondria. Conclusion. Both substances that modulate changes in oxidative stress and the activity of apoptotic processes are recommended for further research as antitumor medicinal agents.


2021 ◽  
Vol 13 (4) ◽  
pp. 365-369
Author(s):  
I. Valchev ◽  
K. Stojanchev ◽  
R. Binev

Abstract. Contamination of poultry feeds with mycotoxins is a global problem faced by poultry industry due to increased demands and availability of poor-quality cereals. The aim of the present study was to evaluate the beneficial effects of a mycotoxin binder (Mycotox NG) on relative weights of internal organs in Pekin ducks with experimental aflatoxicosis. The birds were divided into one control and six experimental groups (n=10) as follows: group І (0 mg/kg AFB1 without Mycotox NG); group ІI (0.5 g/kg Mycotox NG); group ІІI (1.0 g/kg Mycotox NG); group IV (0.2 mg/kg AFB1); group V (0.4 mg/kg AFB1); group VI (0.2 mg/kg AFB1 + 0.5 g/kg Mycotox NG) and group VII (0.4 mg/kg AFB1 + 1.0 g/kg Mycotox NG). Trial duration was 42 days. It was established that ducks fed AFB1-contaminated feed had increased relative weights of liver, kidneys, pancreas, heart, gizzard and proventriculus compared to the control group. At the same time, the relative weights of immunocompetent organs (thymus, spleen and bursa of Fabricius) were reduced. The addition of Mycotox NG to the feed contaminated with AFB1 compensated partly the changes in relative weights of visceral organs. The results from the present study demonstrated that the tested toxin binder could be effective for reduction of toxic effects of aflatoxins in domestic ducks.


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