Correction of oxidative metabolism in myocardium by oligocrine during experimental thyrotoxicosis
M Kvirikashvili1, T Sanikidze2 & D Metreveli1
Numerous number of studies indicate significant role of oxidative stress in the pathogenesis of thyrotoxicosis. The aim of this work was to estimate oxidative metabolism changes in myocardium and effectiveness of olygocrine in the experimental model of thyrotoxicosis.
Methods: Thyrotoxicosis was induced in mature white wistar rats by daily administration of L-thyroxine (100 μg/100 g). We have conducted 3 series of experiments studying: (1) effects of L- thyroxine administered for 10, 15 and 20 days; (2) therapeutic effect of olygocrine on 16th and 21 days of administration against a background of L-thyroxine injections; (3) therapeutic effect of olygocrine on 16th and 21 days of administration (L- thyroxine injections terminated on 10th day). We have studied thyroid status (TSH, FT3, FT4) of animals, oxidative metabolism and NO production in myocardium (by Electron Paramagnetic Resonance and spin-trap methods with X-band radio spectrometer ESR-231). Animals were anaesthetised by sodium ethamonal.
Results: Animals in 1 series present significantly elevated levels of free NO and disturbance in mitochondrial electron-transport chain on NAD.H ubiquinon-oxidoreductase site revealed by enhanced production of semiquinones and nitrosylation of NAD.H dehydrogenase Fe-S centers and leading to increased production of superoxide radicals and lipid peroxides. Oxidative metabolism disturbance results in lowered energogenesis of myocardiocites and affects heart muscle function. In rats treated with oligocrin mitochondrial electron transport in myocardiocites is recuperated, though remains moderately intensified, correlating with FT3 and FT4 levels. Free NO and lipid peroxide levels are moderately elevated.
Conclusions: Increased free radical production during thyrotoxicosis occurs due to thyroid status disturbance resulted in hypercatabolism and intensification of mitochondrial electron transport. Protective effect of oligocrine consists in facilitating both elimination of hypermetabolism and stabilization of thyroid status.