Tatalović Nikola, Vidonja Uzelac Teodora, Oreščanin Dušić Zorana, Nikolić-Kokić Aleksandra, Bresjanac Mara, Blagojević Duško
Department of Physiology, Institute for Biological Research "Siniša Stanković", National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia.
LNPR, Institute of Pathophysiology, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia.
Antioxidants (Basel). 2021 Nov 9;10(11):1792. doi: 10.3390/antiox10111792.
Ibogaine 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 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-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 and β adrenoceptors selective antagonists) and glibenclamide (K sensitive channels inhibitor; only frequency) pre-treatment. In Ca-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-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 channels mediated.
伊波加因的作用是通过细胞受体介导的，其会导致ATP耗竭，随后以剂量和时间依赖性方式产生活性氧（ROS）并提高抗氧化酶活性。由于在此确定了钾通道和β-肾上腺素能受体在ROS细胞回路中的作用，我们探究了它们在伊波加因的抗氧化有效性中的作用。将单剂量的伊波加因（10mg/L，即28.8μmol/L）应用于分离的大鼠子宫（自发和钙刺激），并在4小时内监测其收缩性和抗氧化酶活性。添加伊波加因后，自发活动子宫的振幅和频率立即增加，而普萘洛尔（β和β肾上腺素能受体选择性拮抗剂）和格列本脲（钾敏感通道抑制剂；仅对频率有影响）预处理可阻止这种增加。在钙刺激的子宫中，4小时后伊波加因降低了振幅和频率。普萘洛尔预处理消除了伊波加因引起的振幅降低，而格列本脲则没有效果。在两种类型的活动子宫中，2小时后伊波加因均导致超氧化物歧化酶1（SOD1）减少，过氧化氢酶（CAT）活性增加。在钙刺激的子宫中，2小时后超氧化物歧化酶2（SOD2）活性也降低。4小时后，SOD1活性恢复到基线水平，但谷胱甘肽过氧化物酶（GSH-Px）活性增加。普萘洛尔和格列本脲预处理均消除了观察到的抗氧化酶活性变化，表明伊波加因的抗氧化有效性是由β-肾上腺素能受体和钾通道介导的。
