The Effects of Ibogaine on Uterine Smooth Muscle Contractions: Relation to the Activity of Antioxidant Enzymes

Zorana Oreščanin-Dušić,Jelena Nestorov,Mihajlo Spasić,Nikola Tatalović,Duško Blagojević,Teodora Vidonja-Uzelac,Aleksandra Nikolić-Kokić,Mara Bresjanac,Roman Paškulin,Ana Mijušković

doi:10.1155/2018/5969486

Abstract

Ibogaine is an indole alkaloid originally extracted from the root bark of the African rainforest shrub Tabernanthe iboga. It has been explored as a treatment for substance abuse because it interrupts drug addiction and relieves withdrawal symptoms. However, it has been shown that ibogaine treatment leads to a sharp and transient fall in cellular ATP level followed by an increase of cellular respiration and ROS production. Since contractile tissues are sensitive to changes in the levels of ATP and ROS, here we investigated an ibogaine-mediated link between altered redox homeostasis and uterine contractile activity. We found that low concentrations of ibogaine stimulated contractile activity in spontaneously active uteri, but incremental increase of doses inhibited it. Inhibitory concentrations of ibogaine led to decreased SOD1 and elevated GSH-Px activity, but doses that completely inhibited contractions increased CAT activity. Western blot analyses showed that changes in enzyme activities were not due to elevated enzyme protein concentrations but posttranslational modifications. Changes in antioxidant enzyme activities point to a vast concentration-dependent increase in H2O2 level. Knowing that extracellular ATP stimulates isolated uterus contractility, while H2O2 has an inhibitory effect, this concentration-dependent stimulation/inhibition could be linked to ibogaine-related alterations in ATP level and redox homeostasis.

Highlights

Ibogaine is a psychoactive indole alkaloid derived from the rainforest shrub Tabernanthe iboga, which grows in West Africa
Since contractile tissues are sensitive to changes in the levels of ATP and ROS, here we investigated an ibogaine-mediated link between altered redox homeostasis and uterine contractile activity
We studied the effect of increasing concentrations of ibogaine (1, 2, 5, 10, 15, 20, 40, and 60 mg/l) on an isolated rat uterus in conditions of low and high (Ca2+-stimulated) intensity of contractions, as well as the expression and activity of antioxidant enzymes: cytosolic copper-zinc-containing superoxide dismutase (SOD1), mitochondrial manganese-containing superoxide dismutase (SOD2), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GR)

Summary

Introduction

Ibogaine is a psychoactive indole alkaloid derived from the rainforest shrub Tabernanthe iboga, which grows in West Africa. The pharmacological properties of ibogaine have been known for over 100 years. During the early period of exploration, ibogaine was mostly known for its ability to inspire a sense of wellbeing both mentally and physically. Ibogaine has been used for the treatment of substance abuse because it interrupts drug addiction, relieves withdrawal symptoms, and significantly decreases the desire for cocaine, heroin, alcohol, and most other mind-altering drugs [1,2,3,4]. The pharmacology of ibogaine is quite complex and affects many different neurotransmitter systems simultaneously. Ibogaine binds to several types of receptors: 5-hydroxytryptamine (5-HT), opioid, nicotinic, and N-methyl-D-aspartate (NMDA), as well as dopaminergic and 5-HT transporters and monoamine oxidase (MAO) enzyme [5,6,7]

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