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

Author:

Oreščanin-Dušić Zorana1ORCID,Tatalović Nikola1ORCID,Vidonja-Uzelac Teodora1ORCID,Nestorov Jelena2ORCID,Nikolić-Kokić Aleksandra1ORCID,Mijušković Ana1ORCID,Spasić Mihajlo1ORCID,Paškulin Roman3,Bresjanac Mara4ORCID,Blagojević Duško1ORCID

Affiliation:

1. Department of Physiology, Institute for Biological Research “Siniša Stanković”, University of Belgrade, Despota Stefana 142, 11000 Belgrade, Serbia

2. Department of Biochemistry, Institute for Biological Research “Siniša Stanković”, University of Belgrade, Despota Stefana 142, 11000 Belgrade, Serbia

3. OMI Institute, Trnovska 8, SI-1000 Ljubljana, Slovenia

4. Institute of Pathophysiology, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana, Slovenia

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.

Funder

Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja

Publisher

Hindawi Limited

Subject

Cell Biology,Aging,General Medicine,Biochemistry

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