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Oxidative Medicine and Cellular Longevity
Volume 2018, Article ID 5969486, 10 pages
https://doi.org/10.1155/2018/5969486
Research Article

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

1Department of Physiology, Institute for Biological Research “Siniša Stanković”, University of Belgrade, Despota Stefana 142, 11000 Belgrade, Serbia
2Department of Biochemistry, Institute for Biological Research “Siniša Stanković”, University of Belgrade, Despota Stefana 142, 11000 Belgrade, Serbia
3OMI Institute, Trnovska 8, SI-1000 Ljubljana, Slovenia
4Institute of Pathophysiology, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana, Slovenia

Correspondence should be addressed to Duško Blagojević; sr.ca.gb.ssibi@ejogalbd

Received 17 November 2017; Accepted 28 December 2017; Published 11 February 2018

Academic Editor: Angel Catalá

Copyright © 2018 Zorana Oreščanin-Dušić et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.