ethylthiosulfanylate is alkyl ester of thiosulfoacid and belongs to the class of thiosulfonate compounds. structurally, thiosulfonates are synthetic analogues of natural phytoncides. It is known that, natural organic sulfur-containing compounds are characterized by antioxidant and detoxification properties against heavy metals toxicity. therefore, the purpose of the study was to investigate the influence of ethylthiosulfanylate, as a synthetic analogue of natural phytoncides, on the state of the pro/antioxidant system in the liver of laboratory rats exposed to cr(vI). It was found that ethylthiosulfanylate exposure at a dose 100 mg/kg body weight daily for 14 days led to a decrease in the intensity of increasing of the lipid hydroperoxides (lhP) content in the rat liver caused by cr(vI) action. In addition, ethylthiosulfanylate pretreatment prevented depletion of reduced glutathione (Gsh) pool under the action of potassium dichromate oxidative stress and performed the accumulation of cellular Gsh in rat liver.
Background. The main pathway of Cr(VI) cytotoxicity is activation of oxidative stress in cells of living organisms, resulting in an imbalance of blood biochemical parameters. Our recent studies indicate that S-ethyl-4-aminobenzenethiosulfonate (ETS), which belongs to thiosulfonate compounds, is able to reduce intensity of Cr(VI)-induced oxidative stress in liver tissue of rats. It is known that oxidative stress induced by Cr(VI) causes liver and kidney tissue damage with a subsequent imbalance of blood biochemical parameters. Therefore, the aim of this study was to evaluate the potential ability of ETS to prevent Cr(VI)-induced disorders of some biochemical blood parameters, which are important biomarkers of Cr(VI) intoxication. Materials and Methods. The object of the research was the separate biochemical parameters of the blood of rats with Cr(VI)-induced oxidative stress after prior exposure to ETS. Two experimental groups of male Wistar rats were intoxicated once per day intraperitoneally with K2Cr2O7 dissolved in physiological saline solution for 7 or 14 days. Two other experimental groups were pretreated once per day intragastrically with ETS dissolved in oil before the period of 7 or 14-day K2Cr2O7 intoxication. We measured total protein, creatinine and urea level, as well as determined the activity of aminotransferases in the blood plasma of rats. Results. Intraperitoneal injection of K2Cr2O7 (dissolved in physiological saline solution at a dose of 2.5 mg Cr(VI)/kg body weight) for 7 and 14 days causes a decrease in total protein level and leads to elevation of plasma creatinine level and urea concentration. The activity of blood aminotransferases increases due to Cr(VI) toxicity. The 14-day exposure to ETS (dissolved in oil at a dose 100 mg/kg body weight) prior to the period of Cr(VI) intoxication is characterized by a smaller percentage increase in the level of creatinine, urea and activity of alanine aminotransferase (ALT) in the blood plasma of rats. Conclusion. Cr(VI)-induced toxicity causes an imbalance in biochemical blood parameters. Cr(VI) induces a total protein decrease and leads to an increase in the level of the studied biochemical parameters of blood plasma, which are markers of damage to the liver (aminotransferases) and kidneys (creatinine, urea). In contrast, exposure to ETS for 14 days prior to the period of Cr(VI) intoxication causes percentage decrease in creatinine, urea accumulation and percentage reduction of ALT hyper-activation in the blood of rats. However, the levels of creatinine, urea and ALT activity in this case remained significantly higher than those in the control group. In conclusion, pretreatment with ETS (100 mg/kg) for 2 weeks helps to reduce the level of Cr(VI)-induced disturbances of some blood biochemical parameters, but does not normalize them.
Synthetic water-soluble phenolic antioxidants are known anti-inflammatory chemicals, some of them were shown to induce components of antioxidative defense enzymes NADPH:quinone oxidoreductase (NQO1) and glutathione-S-transferase (GST) via activation of Nrf2 pathway. Our experimental in vivo models have demonstrated an increase of both gstp1 and nqo1 expression in the liver of mice treated with novel organosulfur phenolic compounds TS-12, TS-13, TS-14. Both expression and activity of GSTP1 was dependent on the distance of active thiosulfonate group in para-position from the benzene ring of the above antioxidants. The increase of nqo1 and gstp1 gene expression was mediated by the antioxidant-binding response element (ARE). Our results revealed the role of Nrf2/ARE-dependent transcription regulation in response to the new phenolic antioxidants and suggested possible strategy to improve antioxidative properties of synthetic phenolic compounds.
The aim of our study was to investigate the effect of ethylthiosulfаnylate, a representative of the class of thiosulfonate compounds, in combination with vitamin E on certain biochemical blood parameters, hematological indicators and total Chromium content in liver of rats exposed to Cr(VI). Laboratory rats were divided into 8 groups of 5 animals each. Animals of group I (intact control) were injected daily intraperitoneally with 150 μl of physiological saline solution for 7 days. Rats of III/IV groups received intraperitoneal daily administration of K2Cr2O7 (diluted in physiological saline solution at a dose of 2.5 mg Cr(VI)/kg) for 7/14 days. Animals of the II experimental group were injected daily intragastrically with 1000 μl of sunflower oil for 14 days. Rats of V/VI experimental groups were administrated daily intragastrically with 1000 μl of an oil solution of vitamin E (20 mg/kg)/vitamin E (20 mg/kg) in combination with ethylthiosulfаnylate (100 mg/kg) for 14 days. Animals of VII/VIII experimental groups were injected daily intragastrically with 1000 μl of an oil solution of vitamin E (20 mg/kg) in combination with ethylthiosulfаnylate (100 mg/kg) for 14 days, after which a 7-day/14-day period of intraperitoneal K2Cr2O7 administration was performed. Exposure to Cr(VI) led to a decrease in the number of erythrocytes, leukocytes, content of hemoglobin, phospholipids, total protein against the background of the accumulation of total lipids, mono- and diglycerides, non-esterified fatty acids, and creatinine in blood of rats. Chromium concentration significantly increased in the liver of rats after administration of Cr(VI). The combined effect of vitamin E and ethylthiosulfаnylate contributed to the partial compensation of Cr(VI)-induced disturbances of the number of leukocytes and content of total proteins, phospholipids, non-esterified fatty acids in blood of rats. Vitamin E and ethylthiosulfаnylate pretreatment also contributed to the reduction of the percentage accumulation of Chromium in liver of rats injected with Cr(VI).
Ethylthiosulfanylate (ETS) is synthetic organosulfur compound and belongs to the class of thiosulfonates, which are the structural analogues of natural BACs of plant origin. Thiosulfonates and ETS in particular affect the regulation of pro/antioxidant status, lipid and protein metabolism in the tissues of laboratory rats. Cr(VI) compounds are characterized by potent prooxidant properties and high toxicity for cells of living organisms. The toxic effect of Cr(VI)-induced oxidative stress is accompanied by lipid metabolism disorders and the correction methods have not been sufficiently studied. The aim of our study was to investigate the effect of ETS on some indicators of lipid metabolism in blood plasma of rats under the action of K2Cr2O7-induced toxicity. Animals were divided into 7 groups. Animals of group I injected daily intraperitoneally with 150 μl of physiological solution for 7 days. Experimental groups III and IV were administered daily intraperitoneally with K2Cr2O7 in a dose of 2.5 mg Cr(VI)/kg body weight, for 7 (group III) and 14 days (group IV). Rats of group II received intragastric injection of 1000 μl of oil daily for 14 days, than animals were injected daily intraperitoneally with 150 μl of physiological solution for 7 days. Experimental group V was intragastrically injected with ETS oily solution at a rate of 100 mg/kg of body weight daily for 14 days, than animals were injected intraperitoneally 150 μl of physiological solution daily for 7 days. Animals of groups VI and VII were intragastrically administered with ETS oily solution at a rate of 100 mg/kg of body weight daily for 14 days, than animals were injected intraperitoneally daily K2Cr2O7 in a dose of 2.5 mg Cr(VI)/kg body weight, for 7 (group VI) and 14 days (group VII). Rats were decapitated under thiopental anesthesia, after which blood was taken and divided into erythrocytes and plasma. The Cr(VI) action for 7 (group III) and 14 days (group IV) led to an increase in the content of total lipids and triglycerides in the blood plasma of rats, but the percentage of nonesterified cholesterol decreased. ETS partially compensates the Cr(VI)-induced toxicity by reducing the intensity of total lipids (groups VI, VII) and triglycerides (group VI) accumulation.
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