Ibogaine-mediated ROS/antioxidant elevation in isolated rat uterus is β-adrenergic receptors and K$_{ATP}$ channels mediated

Tatalović, Nikola (author), Vidonja-Uzelac, Teodora (author), Oreščanin-Dušić, Zorana (author), Nikolić-Kokić, Aleksandra (author), Bresjanac, Mara (author), Blagojević, Duško (author)

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$_{ATP}$ 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.

• Language: English
• Keywords: ibogaine, K$_{ATP}$ channels, glibenclamide, β-adrenergic receptors, propranolol, antioxidative enzymes, superoxide dismutase, catalase, uterus, contractility
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2021
• Number of pages: 16 str.
• Numbering: Vol. 10, iss. 11, art. 1792
• PID: 20.500.12556/RUL-137417
• ISSN on article: 2076-3921
• DOI: 10.3390/antiox10111792
• COBISS.SI-ID: 140497923
• Publication date in RUL: 16.06.2022

Record is a part of a journal

• Title: Antioxidants
• Shortened title: Antioxidants
• Publisher: MDPI
• ISSN: 2076-3921
• COBISS.SI-ID: 522976025

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: ibogain, K$_{ATP}$ kanali, glibenklamid, β-adrenergični receptorji, propranolol, antioksidativni encimi, superoksid dismutaza, katalaza, maternica, kontraktilnost

Projects

• Funder: MESTD - Ministry of Education, Science and Technological Development of Republic of Serbia
• Project number: 451-03-68/2020-14/200007

• Funder: ARRS - Slovenian Research Agency
• Project number: P3-0171
• Name: Plastičnost živčevja v fizioloških in patofizioloških razmerah