Diabetes is widely spread among people of active age and is characterized by the development of severe complications which made patients invalid. That is why it is extremely need to work out new approaches to prophylaxis and treatment of those complications. Experimental streptozotocin-induced diabetes is used for the investigations of glucosotoxic effects along with the screening of anti-diabetes pharmacons.
Aim of the research was confined to the investigations of the hepatocytes membrane state under conditions of experimental diabetes and its treatment with derivatives of oxietilyden-diphosphonate — germanate (NicH)2 [Ge(OH)2 (Oedph)]. H2O (MIGU-4)with molar mass of 593 G/mol.
Material and methods of investigation. Exeprimental diabetes was modeled via i. p. streptozotocin (STZ) (“Sigma Aldrich ru”, 50 mg/kg) administration. MIGU-4 was adiministered in a dosage of 25.0 mg/kg, i. p. Next fluorescence zonds have been explored: universal one — 1 — anilinenaphtaline — 8-sulphonate (1,8-АNS), which bears electronegativity and is diving only at the depth of superficial layer of lipids; hydrophobic one — N — phenyl-1-naphtalamine (1-PNА), which contains sulphate groups and is able to dive deeply into lipid bilayer (up to 8 C from three methylaminogroups of phospholipids). The next indices have been measured: fluorescence intensity (Fmol), specific number of zonds binding (N), constant of binding (Кb) as well as dissociation constant (Kd) of zonds. Membranes were got via liver homogenates centrifugation, with the ourity checking via light mictroscopy. The fluorescence was verified with spectrophotometer “Opton” (Germany) at the next wave lengths: 360 and 480 nm for ANS; 350 and 420 nm for 1-PNA.
Results of invetsigation. The level of glucose in blood was (15.14±0.83); (14.02±0.76), аnd (10.25±0.39) mmol/L in two weeks, one, and three months from the moment of MIGU-4 administration correspondently. The level of glucose in insulin — treated rats at analogous time of observation was (10.37±0.95); (8.17±0.64) and (7.89±0.39) mmol/L correspondently. In STZ-diabetes Fmol of 1,8-ANS zond was reduced in more eight times when compared with the control. At the same time Kb and N increased five times while the constant of dissociation (Kd) decreased by more than four times. In STZ diabetes the Fmol of 1-PNA zond was reduced by 61.2%, while N raised more than two times pertained to the control data. MIGU-4 administration induced pronounced correction of listed deteriorations, while those ones continue kept differences when compared with control data. The combined usage of MIGU-4 and insulin investigated indices were not different from control ones.
Conclusions. The experimental STZ-induced diabetes is characterized by substantial deterioration of morphofunctional state of lipid mitochondria membrane, which are more pronounced oin the superficial layer of lipids. The usage of niacin — oxietilyden-diphosphonate-germanate (NicH)2 [Ge(OH)2 (Oedph)]. H2O (MIGU-4) ameliorated the diabetes-induced changes of lipid bilayer and increased the therapeutic effect of insuline.