Ibogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and KATP Channels Mediated.

A single dose of ibogaine (28.8 μmol/L) applied to isolated rat uterus altered contractility and antioxidant enzyme activity over four hours. In spontaneously contracting uteri, ibogaine immediately increased contraction amplitude and frequency, effects blocked by propranolol (β-adrenoceptor antagonist) and glibenclamide (KATP channel inhibitor, for frequency only). In calcium-stimulated uteri, ibogaine decreased amplitude and frequency after four hours; propranolol prevented the amplitude reduction, but glibenclamide had no effect. Ibogaine reduced superoxide dismutase 1 (SOD1) activity and increased catalase (CAT) activity after two hours in both uterus types, and in calcium-stimulated uteri also reduced SOD2 activity. After four hours, SOD1 returned to baseline while glutathione peroxidase (GSH-Px) activity rose. Pre-treatment with propranolol or glibenclamide abolished these enzyme changes, indicating ibogaine's pro-antioxidant effects are mediated by β-adrenergic receptors and KATP channels.

Study at a glance

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.