Ibogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and KATP Channels Mediated.
Antioxidants (Basel, Switzerland) – November 09, 2021
Source: PubMed
Summary
A recent finding illuminates how ibogaine influences the body's natural defenses. Investigating isolated rat uterus, scientists explored how ibogaine affects contractility and antioxidative enzymes. Ibogaine immediately increased uterus contractions, an effect prevented by propranolol, targeting β-adrenergic receptors, and glibenclamide, affecting KATP channels. Crucially, ibogaine boosted antioxidative enzymes like catalase while affecting superoxide dismutase. Both propranolol and glibenclamide blocked these beneficial enzyme responses, revealing ibogaine's pro-antioxidant effectiveness is mediated by β-adrenergic receptors and KATP channels.
Abstract
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 KATP 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 Ca2+-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 (β1 and β2 adrenoceptors selective antagonists) and glibenclamide (KATP sensitive channels inhibitor; only frequency) pre-treatment. In Ca2+-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 Ca2+-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 KATP channels mediated.