Hybrid organotin compounds — modulators of apoptotic processes in the liver when administered once and repeatedly to Wistar rats

Abstract

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.