This study investigates the effects of long-term treatment with sulodexide (SLX) on norepinephrine (NE)-induced contractions, acetylcholine(Ach)-induced relaxations, acute cyclooxygenase blockade by diclofenac (DIC) in isolated femoral arteries (FA) and the parameters of oxidative phosporylation in liver mitochondria. 15-weeks old Wistar rats were divided into four groups: control (C; injected with saline solution), treated control (C+SLX), diabetic (DM) and treated diabetic (DM+SLX). Diabetes was induced with a single i.v. dose of streptozotocin (STZ) 45 mg.kg-1. SLX was administered i.p., at dose 100 IU.kg-1 daily for 5 weeks. Vascular responses of isolated femoral arteries were measured using Mulvany-Halpern myograph. Respiratory function of the mitochondria was determined using voltamperometric method on oxygraph Gilson. In diabetic rats the amplitude of maximal response to NE was elevated. DIC pretreatment decreased the amplitudes of NE-induced contractions in all groups of rats. SLX treatment decreased sensitivity of FA to NE and caused higher relaxatory responses to Ach in C and DM. Oxygen consumption and phosphorylation rates ([QO2(S3)], [QO2(S4)] and (OPR)) and respiratory control ratio (RCR) were decreased in the mitochondria of DM rats. Mitochondria of C rats were not affected with SLX treatment. Administration of SLX in DM rats was associated with increase of RCR, other parameters were not affected. Our findings suggest that SLX treatment might be associated with vasculoprotective effects during diabetes and improvement of mitochondrial function., L. Dobiaš, M. Petrová, R. Vojtko, O. Uličná, O. Vančová, V. Kristová., and Obsahuje bibliografii
The aim of present study was to investigate functional and physical alterations in membranes of heart mitochondria that are associated with remodeling of these organelles in acute phase of streptozotocin-induced diabetes and to elucidate the role of these changes in adaptation of the heart to acute streptozotocin-induced diabetes (evaluated 8 days after single dose streptozotocin application to male Wistar rats). Action of free radicals on the respiratory chain of diabetic-heart mitochondria was manifested by 17 % increase (p<0.05) in oxidized form of the coenzyme Q10 and resulted in a decrease of states S3 and S4 respiration, the respiratory control index, rate of phosphorylation (all p<0.01) and the mitochondrial transmembrane potential (p<0.05), but the ADP/O ratio decreased only moderately (p>0.05). On the contrary, membrane fluidity and the total mitochondrial Mg2+-ATPase activity increased (both p<0.05). In diabetic heart mitochondria, linear regression analysis revealed a reciprocal relationship between the increase in membrane fluidity and decrease in trans-membrane potential (p<0.05, r = 0.67). Changes in membrane fluidity, transmembrane potential, Mg2+-ATPase activity and the almost preserved ADP/O ratio appear as the manifestation of endogenous protective mechanisms participating in the functional remodeling of mitochondria which contributes to adaptation of the heart to diabetes., M. Ferko, D. Habodászová, I. Waczulíková, J. Mujkošová, J. Kucharská, L. Šikurová, B. Ziegelhöffer, J. Styk, A. Ziegelhöffer., and Obsahuje bibliografii a bibliografické odkazy
Using high-resolution oxygraphy, we tested the changes of various parameters characterizing the mitochondrial energy provision system that were induced by peroxidative damage. In the presence of succinate as respiratory substrate, 3 mM t-butyl hydroperoxide increased respiration in the absence of ADP, which indicated partial uncoupling of oxidative phosphorylation. Low activity of coupled respiration was still maintained as indicated by the ADP-activated and oligomycin-inhibited respiration. However, during the incubation the phosphorylative capacity decreased as indicated by the continuous decrease of the mitochondrial membrane potential. Under these experimental conditions the maximum capacity of the succinate oxidase system was inhibited by 50 % in comparison with values obtained in the absence of t-butyl hydroperoxide. Our data thus indicate that the oxygraphic evaluation of mitochondrial function represents a useful tool for evaluation of changes participating in peroxidative damage of cell energy metabolism., P. Křiváková, A. Lábajová, Z. Červinková, Z. Drahota., and Obsahuje bibliografii a bibliografické odkazy