Ibogaine-mediated ROS/antioxidant elevation in isolated rat uterus is β-adrenergic receptors and K$_{ATP}$ channels mediatedTatalović, Nikola (Avtor) Vidonja-Uzelac, Teodora (Avtor) Oreščanin-Dušić, Zorana (Avtor) Nikolić-Kokić, Aleksandra (Avtor) Bresjanac, Mara (Avtor) Blagojević, Duško (Avtor) ibogaineK$_{ATP}$ channelsglibenclamideβ-adrenergic receptorspropranololantioxidative enzymessuperoxide dismutasecatalaseuteruscontractilityIbogaine effects are mediated by cellular receptors, ATP depletion followed by ROS production and antioxidant enzyme activity elevation in a dose and time dependent manner. Since the role of K$_{ATP}$ channels and β-adrenoceptors in ROS cellular circuit was established here we explored their role in ibogaine pro-antioxidant effectiveness. Single dose of ibogaine (10 mg/L i.e., 28.8 µmol/L) was applied to isolated rat uterus (spontaneous and Ca$^{2+}$-stimulated) and contractility and antioxidant enzymes activity were monitored during 4 h. Ibogaine increased amplitude and frequency of spontaneous active uteri immediately after addition that was prevented by propranolol (β$_1$ and β$_2$ adrenoceptors selective antagonists) and glibenclamide (K$_{ATP}$ sensitive channels inhibitor; only frequency) pre-treatment. In Ca$^{2+}$-stimulated uteri, ibogaine decreased both amplitude and frequency after 4 h. Pre-treatment with propranolol abolished ibogaine induced amplitude lowering, while glibenclamide had no effect. In both types of active uterus, ibogaine induced a decrease in SOD1 and an increase in CAT activity after 2 h. In Ca$^{2+}$-stimulated uterus, there was also a decrease of SOD2 activity after 2 h. After 4 h, SOD1 activity returned to the baseline level, but GSH-Px activity increased. Pre-treatment with both propranolol and glibenclamide abolished observed changes of antioxidant enzymes activity suggesting that ibogaine pro-antioxidative effectiveness is β-adrenergic receptors and K$_{ATP}$ channels mediated.20212022-06-16 10:11:40Članek v reviji137417sl