Effects of ibogaine per os treatment on redox homeostasis in rat kidney

Authors

  • Teodora Vidonja Uzelac Department of Physiology, Institute for Biological Research “Siniša Stanković”, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade http://orcid.org/0000-0003-3700-688X
  • Nikola Tatalović Department of Physiology, Institute for Biological Research “Siniša Stanković”, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade http://orcid.org/0000-0002-0745-8845
  • Milica Mijović Institute of Pathology, Faculty of Medicine, University of Priština, Anri Dinana bb, 38220 Kosovska Mitrovica
  • Aleksandra Nikolić-Kokić Department of Physiology, Institute for Biological Research “Siniša Stanković”, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade http://orcid.org/0000-0002-1116-2035
  • Zorana Oreščanin-Dušić Department of Physiology, Institute for Biological Research “Siniša Stanković”, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade http://orcid.org/0000-0002-2772-0134
  • Mara Bresjanac Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1001 Ljubljana
  • Duško Blagojevic Department of Physiology, Institute for Biological Research “Siniša Stanković”, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade http://orcid.org/0000-0001-6338-2833

Keywords:

ibogaine, kidney, antioxidant enzymes, lipid peroxidation, proximal tubules

Abstract

Paper description:

  • Ibogaine in vivo induces liver glycogen depletion, provokes mild oxidative stress and activates antioxidant enzymes.
  • We examined the in vivo effects of a single per os dose of ibogaine (1 or 20 mg/kg) on the morphology and antioxidative system of rat kidney. Ibogaine applied at a dose of 1 mg/kg elevated superoxide dismutase 1 activity, which was followed by a decrease in glutathione reductase activity, which was also decreased after application of 20 mg/kg, suggesting disturbed redox homeostasis. Ibogaine treatment with both doses provoked moderate changes in kidney morphology.
  • These findings indicate a precautionary approach with ibogaine use regarding kidneys.

Abstract: Our previous results showed that a single oral dose (1 or 20 mg/kg body weight) of the anti-addiction agent ibogaine induced in rats 6 and 24 h after administration glycogenolytic activity in hepatocytes, followed by a mild oxidative stress. In this work, we examined the in vivo effect of the same doses of ibogaine on rat kidney morphology, antioxidant enzyme (superoxide dismutases (SOD 1 and 2), catalase, glutathione peroxidase, glutathione reductase (GR) and glutathione-S-transferase) activities, and oxidative stress (TBARS) and redox (-SH groups) parameters. The dose of 1 mg/kg ibogaine induced an elevation in SOD1 activity and decreased GR activity after 6 and 24 h. GR activity was decreased at 6 and 24 h after 20 mg/kg ibogaine administration, suggesting changed redox homeostasis. After 24 h, we observed an increase in moderate morphological changes, without changes in urinalyses, indicating that kidney function was not measurably affected. Nevertheless, kidney-function monitoring during and following ibogaine use in human subjects is advisable.

https://doi.org/10.2298/ABS190208006V

Received: February 8, 2019; Revised: February 17, 2019; Accepted: February 19, 2019; Published online: February 21, 2019

How to cite this article: Vidonja Uzelac T, Tatalović N, Mijović M, Nikolić-Kokić A, Oreščanin-Dušić Z, Bresjanac M, Blagojević D. Effects of ibogaine per os treatment on redox homeostasis in rat kidney. Arch Biol Sci. 2019;71(2):245-52.

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References

Popik P, Layer R, Skolnick P. 100 years of ibogaine: neurochemical and pharmacological actions of a putative anti-addictive drug. Pharmacol Rev. 1995;47(2):235-53.

Alper K, Lotsof H, Kaplan C. The ibogaine medical subculture. J Ethnopharmacol. 2008;115(1):9-24.

Sheppard S. A preliminary investigation of ibogaine: case reports and recommendations for further study. J Subst Abuse Treat. 1994;11(4):379-85.

Schep L, Slaughter R, Galea S, Newcombe D. Ibogaine for treating drug dependence. What is a safe dose? Drug Alcohol Depend. 2016;166:1-5.

Glue P, Winter H, Garbe K, Jakobi H, Lyudin A, Lenagh-Glue Z, Hung CT. Influence of CYP2D6 activity on the pharmacokinetics and pharmacodynamics of a single 20 mg dose of ibogaine in healthy volunteers. J Clin Pharmacol. 2015;55(6):680-7.

Vidonja Uzelac T, Tatalović N, Mijović M, Koželj G, Nikolić-Kokić A, Oreščanin-Dušić Z, Bresjanac M, Blagojević D. Effects of ibogaine per os treatment on redox homeostasis in rat liver and erythrocytes. Arch Biol Sci. 2018;DOI:10.2298/ABS180918055V.

Paškulin R, Jamnik P, Obermajer N, Slavić M, Štrukelj B. Induction of energy metabolism related enzymes in yeast Saccharomyces cerevisiae exposed to ibogaine is adaptation to acute decrease in ATP energy pool. Eur J Pharmacol. 2010;627(1-3):131-5.

Nikolić-Kokić A, Oreščanin-Dušić Z, Spasojević I, Slavić M, Mijušković A, Paškulin R, Miljević Č, Spasić M, Blagojević D. Ex vivo effects of ibogaine on the activity of antioxidative enzymes in human erythrocytes. J Ethnopharmacol. 2015;164:64-70.

Paškulin R, Jamnik P, Živin M, Raspor P, Štrukelj B. Ibogaine affects brain energy metabolism. Eur J Pharmacol. 2006;552(1-3):11-4.

Oreščanin-Dušić Z, Tatalović N, Vidonja-Uzelac T, Nestorov J, Nikolić-Kokić A, Mijušković A, Spasić M, Paškulin R, Bresjanac M, Blagojević D. The effects of ibogaine on uterine smooth muscle contractions: relation to the activity of antioxidant enzymes. Oxid Med Cell Longev. 2018;2018:5969486.

Paškulin R, Jamnik P, Danevčič T, Koželj G, Krašovec R, Krstić-Milošević D, Blagojević D, Štrukelj B. Metabolic plasticity and the energy economizing effect of ibogaine, the principal alkaloid of Tabernanthe iboga. J Ethnopharmacol. 2012;143(1):319-24.

Kubiliene A, Sveikata A, Zevzikovas A, Sadauskiene I, Ivanov L. Investigation into pharmacokinetic properties of active alkaloid ibogaine and its metabolite noribogaine. Acta Pol Pharm. 2017;74(5):1591-7.

Misra H, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem. 1972;247(10):3170-5.

Beutler E. Red cell metabolism: a manual of biochemical methods. 3rd ed. New York: Grune and Stratton; 1982. 102 p.

Paglia D, Valentine W. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967;70(1):74-7.

Glatzle D, Vuilleumier J, Weber F, Decker K. Glutathione reductase test with whole blood, a convenient procedure for the assessment of the riboflavin status in humans. Experientia. 1974;30(6):665-8.

Habig N, Pabst M, Jakoby N. GST: 1st enzymatic step in mercapturic acid formation. J Biol Chem. 1974;249:7130-9.

Rehncrona S, Smith D, Akesson B, Westerberg E, Siesjo B. Peroxidative changes in brain cortical fatty acids and phospholipids, as characterized during Fe2+- and ascorbic acid-stimulated lipid peroxidation in vitro. J Neurochem. 1980;34(6):1630-8.

Ellman G. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959;82(1):70-7.

Lowry O, Rosebrough N, Farr A, Randall R. Protein measurement with folin phenol reagent. J Biol Chem. 1951;193(1):265-75.

Luna L. G. Manual of histologic staining methods of the armed forces institute of pathology. 3rd ed. New York: McGraw-Hill; 1968.

Hinkle E, Wiersma W, Jurs G. Applied statistics for behavioral sciences. 5th ed. Boston: Houghton Mifflin Company; 2002.

Ralto KM, Parikh SM. Mitochondria in acute kidney injury. Semin Nephrol. 2016; 36(1):8-16.

Nikolić-Kokić A, Mijušković A, Tatalović N, Nestorov J, Miler M, Oreščanin-Dušić Z, Nikolić M, Milošević V, Blagojević D, Spasić M, Miljević Č. Effects of antipsychotic drug administration on antioxidative defense enzymes in male rat kidney. J Toxicol Environ Health. A 2016;79(20):905-11.

Alper K. Ibogaine: A Review. Alkaloids Chem Biol. 2001;56:1-38.

Papadodima SA, Dona A, Evaggelakos CI, Goutas N, Athanaselis SA. Ibogaine related sudden death: a case report. J Forensic Leg Med. 2013;20(7):809-11.

Kubiliene A, Ivanauskas L, Kiliuviene G, Marksiene R, Sadauskiene I, Ivanov L. Cumulation of Tabernanthe Iboga alkaloid and its metabolite in organs of mice. J Med Plants Res. 2012;6(11):2194-9.

Kontrimaviciute V, Mathieu O, Mathieu-Daude JC, Vainauskas P, Casper T, Baccino E, Bressolle FM. Distribution of ibogaine and noribogaine in a man following poisoning involving root bark of the Tabernanthe Iboga scrub. J Anal Toxicol. 2006;30(7):434-40.

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Published

2019-06-04

How to Cite

1.
Vidonja Uzelac T, Tatalović N, Mijović M, Nikolić-Kokić A, Oreščanin-Dušić Z, Bresjanac M, Blagojevic D. Effects of ibogaine per os treatment on redox homeostasis in rat kidney. Arch Biol Sci [Internet]. 2019Jun.4 [cited 2024Dec.22];71(2):245-52. Available from: https://serbiosoc.org.rs/arch/index.php/abs/article/view/3984

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