Ibogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and K<sub>ATP</sub> Channels Mediated

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<sub>ATP</sub> channels and β-adrenoceptors in ROS cellular circuit was established here we expl...

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Autores principales:	Nikola Tatalović, Teodora Vidonja Uzelac, Zorana Oreščanin Dušić, Aleksandra Nikolić-Kokić, Mara Bresjanac, Duško Blagojević
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ibogaine K<sub>ATP</sub> channels glibenclamide β-adrenergic receptors propranolol antioxidative enzymes Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/0f7b858f2c504877853fbb4030fb2d9b
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spelling	oai:doaj.org-article:0f7b858f2c504877853fbb4030fb2d9b2021-11-25T16:28:40ZIbogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and K<sub>ATP</sub> Channels Mediated10.3390/antiox101117922076-3921https://doaj.org/article/0f7b858f2c504877853fbb4030fb2d9b2021-11-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1792https://doaj.org/toc/2076-3921Ibogaine 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<sub>ATP</sub> 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<sup>2+</sup>-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<sub>1</sub> and β<sub>2</sub> adrenoceptors selective antagonists) and glibenclamide (K<sub>ATP</sub> sensitive channels inhibitor; only frequency) pre-treatment. In Ca<sup>2+</sup>-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<sup>2+</sup>-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<sub>ATP</sub> channels mediated.Nikola TatalovićTeodora Vidonja UzelacZorana Oreščanin DušićAleksandra Nikolić-KokićMara BresjanacDuško BlagojevićMDPI AGarticleibogaineK<sub>ATP</sub> channelsglibenclamideβ-adrenergic receptorspropranololantioxidative enzymesTherapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1792, p 1792 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ibogaine K<sub>ATP</sub> channels glibenclamide β-adrenergic receptors propranolol antioxidative enzymes Therapeutics. Pharmacology RM1-950
spellingShingle	ibogaine K<sub>ATP</sub> channels glibenclamide β-adrenergic receptors propranolol antioxidative enzymes Therapeutics. Pharmacology RM1-950 Nikola Tatalović Teodora Vidonja Uzelac Zorana Oreščanin Dušić Aleksandra Nikolić-Kokić Mara Bresjanac Duško Blagojević Ibogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and K<sub>ATP</sub> Channels Mediated
description	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<sub>ATP</sub> 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<sup>2+</sup>-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<sub>1</sub> and β<sub>2</sub> adrenoceptors selective antagonists) and glibenclamide (K<sub>ATP</sub> sensitive channels inhibitor; only frequency) pre-treatment. In Ca<sup>2+</sup>-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<sup>2+</sup>-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<sub>ATP</sub> channels mediated.
format	article
author	Nikola Tatalović Teodora Vidonja Uzelac Zorana Oreščanin Dušić Aleksandra Nikolić-Kokić Mara Bresjanac Duško Blagojević
author_facet	Nikola Tatalović Teodora Vidonja Uzelac Zorana Oreščanin Dušić Aleksandra Nikolić-Kokić Mara Bresjanac Duško Blagojević
author_sort	Nikola Tatalović
title	Ibogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and K<sub>ATP</sub> Channels Mediated
title_short	Ibogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and K<sub>ATP</sub> Channels Mediated
title_full	Ibogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and K<sub>ATP</sub> Channels Mediated
title_fullStr	Ibogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and K<sub>ATP</sub> Channels Mediated
title_full_unstemmed	Ibogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and K<sub>ATP</sub> Channels Mediated
title_sort	ibogaine-mediated ros/antioxidant elevation in isolated rat uterus is β-adrenergic receptors and k<sub>atp</sub> channels mediated
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0f7b858f2c504877853fbb4030fb2d9b
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Ibogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and K<sub>ATP</sub> Channels Mediated

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