Прегледај по Аутор "Blagojevic, Dusko"

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    Fullerenol C60(OH)24 nanoparticles decrease relaxing effects of dimethyl sulfoxide on rat uterus spontaneous contraction
    (Springer, 2013) Slavic, Marija; Djordjevic, Aleksandar; Radojicic, Ratko; Milovanovic, Slobodan; Orescanin-Dusic, Zorana; Rakocevic, Zlatko; Spasic, Mihajlo B.; Blagojevic, Dusko
    Dimethyl sulfoxide (DMSO) is a widely used solvent and cryoprotectant that can cause impaired blood flow, reduction in intracranial pressure, tissue edema, inflammatory reactions, inhibition of vascular smooth muscle cell migration and proliferation, processes which can lead to atherosclerosis of the coronary, peripheral and cerebral circulation. Although the adverse effects are rare when DMSO is administered in clinically established concentrations, there is no safe antagonist for an overdose. In this work, we treated isolated spontaneous and calciuminduced contractile active rat uteri (Wistar, virgo intacta), with DMSO and fullerenol C60(OH)24 nanoparticle (FNP) in DMSO. FNP is a water-soluble derivative of fullerene C60. Its size is a 1.1 nm in diameter and is a very promising candidate for a drug carrier in nanomedicine. FNP also displays free radical scavenging activity. DMSO decreased both spontaneous and calcium-induced contractions. In contrast, FNP only decreased spontaneous contraction. FNP decreased copper–zinc superoxide dismutase activity and prevented the DMSO-induced increase in glutathione reductase activity. Atomic force microscopy detected that FNP aggregated with calcium ions. Our results indicate that FNP has properties that make it a good candidate to be a modulator of DMSO activity which could minimize side effects of the latter.
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    Reversible Oxidation ofMyometrial Voltage-Gated Potassium Channels with Hydrogen Peroxide
    (Hindawi, 2012) Appiah, Isabella; Nikolic-Kokic, Aleksandra; Orescanin-Dusic, Zorana; Radojicic, Ratko; Milovanovic, Slobodan; Spasic, Mihajlo; Blagojevic, Dusko
    The uteri, spontaneously active or Ca2+ (6mM) induced, were allowed to equilibrate, and to inhibit voltage-gated potassium (KV ) channels 1mM4-amino pyridine (4-AP) was applied for 15 min before addingH2O2 . H2O2 was added cumulatively: 2 μM, 20 μM, 200 μM, 400 μM, and 3mM. Average time for H2O2 concentrations (2, 20, 200, and 400) μM to reach its full effect was 15 min. H2O2 3mMhad a prolonged effect and therefore was left to act for 30 min. Two-way ANOVA showed significant differences in time dependency between spontaneous and Ca2+-induced rat uteri after applying 3mMH2O2 (type of contraction, P = 0.0280), but not 400 μMH2O2 (P = 0.9271). Our results indicate that H2O2 oxidises channel intracellular thiol groups and activates the channel, inducing relaxation. Cell antioxidative defence system quickly activates glutathione peroxidase (GSHPx) defence mechanism but not catalase (CAT) defence mechanism. Intracellular redox mechanisms repair the oxidised sites and again establish deactivation of KV channels, recuperating contractility. In conclusion, our results demonstrate that KV channels can be altered in a timedependent manner by reversible redox-dependent intracellular alterations.
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    THE IMPORTANCE OF POTASSIUM CHANNELS IN THE MECHANISM OF THE RELAXING EFFECT OF PENTOXIFYLLINE ON ISOLATED RAT UTERI
    (University of Kragujevac, Faculty of Science, 2013) Milovanovic, Slobodan R.; Kordic-Bojinovic, Jelena; Djordjevic, Stevanka; Drakul, Dragana; Sokolovic, Dragana; Miletic, Natasa; Blagojevic, Dusko
    Background. Pentoxifylline is a methylxanthine derivative that is used to treat peripheral vascular disease. One of the mechanisms of action of pentoxifylline is the vasodilatation of blood vessels. Th is study examined the eff ect of increasing pentoxifylline concentrations on the contractility of isolated rat uteri in the presence of a potassium channel antagonist. Methods. Th e uteri were isolated from virgin Wistar rats (180-220 g) and suspended in an isolated organ bath chamber containing De Jalon’s solution and aerated with 95% O2 and 5% CO2. Th e temperature was maintained at 37ºC. Isometric contractions were recorded using an isometric force transducer (Ugo Basile). The preload of the preparation was approximately 1 g. Th e uteri were allowed to contract spontaneously or in the presence of Ca2+ (0.018 and 0.36 mM) and acetylcholine (ACh) and were treated with pentoxifylline. Results. Pentoxifylline caused concentration-dependent inhibition of spontaneous rhythmic uterine activity and uterine activity caused by calcium Ca2+ (0.018 mM and 0,36 mM). We showed that the inhibitory eff ects of pentoxifylline depend on the type of muscle contractions activated and that the inhibitory eff ect is signifi cantly stronger for spontaneous rhythmic activity and forin Ca2 -induced contractions of isolated rat uteri+. Th e relaxing eff ect of pentoxifylline depends on the calcium concentration in the medium. Pentoxifylline exerted the weakest relaxant eff ects on contractions induced by acetylcholine. In contrast to methylene blue, tetraethylammonium, or 4-aminopyridine, glibenclamide did not antagonise the relaxing eff ect of pentoxifylline on isolated rat uteri.. Conclusion. Th e results obtained suggest that the mechanism of action of pentoxifylline does not lead to the opening of KATP channels. However, the opening of BKCa and voltage-dependent Ca2+ channels had some role, but to varying degrees, in the mechanism of the relaxing eff ect of pentoxifylline on the spontaneous rhythmic activity and calcium-induced tractions of isolated rat uteri. Our results provide additional confi rmation of the dominance of the NO/cGMP signalling pathway in the mechanism of the relaxing eff ect of pentoxifylline (because the presence of methylene blue signifi cantly antagonised this eff ect) in relation to the opening of potassium channels, especially KATP channels. Th ese results indicate that pentoxifylline could be a potential tocolytic drug.