Ibogaine Has Sex-Specific Plasma Bioavailability, Histopathological and Redox/Antioxidant Effects in Rat Liver and Kidneys: A Study on Females
Nikola Tatalović,
Teodora Vidonja Uzelac,
Milica Mijović,
Gordana Koželj,
Aleksandra Nikolić-Kokić,
Zorana Oreščanin Dušić,
Mara Bresjanac,
Duško Blagojević
Affiliations
Nikola Tatalović
Department of Physiology, Institute for Biological Research “Siniša Stanković”—National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia
Teodora Vidonja Uzelac
Department of Physiology, Institute for Biological Research “Siniša Stanković”—National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia
Milica Mijović
Institute of Pathology, Faculty of Medicine, University of Priština, Anri Dinana bb, 38220 Kosovska Mitrovica, Serbia
Gordana Koželj
Institute of Forensic Medicine, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia
Aleksandra Nikolić-Kokić
Department of Physiology, Institute for Biological Research “Siniša Stanković”—National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia
Zorana Oreščanin Dušić
Department of Physiology, Institute for Biological Research “Siniša Stanković”—National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia
Mara Bresjanac
Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia
Duško Blagojević
Department of Physiology, Institute for Biological Research “Siniša Stanković”—National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia
Ibogaine induces rapid changes in cellular energetics followed by the elevation of antioxidant activities. As shown earlier in male rats, ibogaine treatment with both 1 and 20 mg/kg b.w. per os led to significant glycogenolytic activity in the liver. In this work, female rats treated with the same doses of ibogaine per os displayed lower liver glycogenolytic activity relative to males, dilatation of the central vein and branches of the portal vein, and increased concentration of thiols 6 h after treatment. These changes were followed by increased catalase activity and lipid peroxidation, and decreased xanthine oxidase activity after 24 h. In kidneys, mild histopathological changes were found in all treated animals, accompanied by a decrease of glutathione reductase (after 6 and 24 h at both doses) and an increase of catalase (6 h) and xanthine oxidase activity (6 and 24 h). Ibogaine did not affect antioxidant enzymes activity in erythrocytes. Bioavailability of ibogaine was two to three times higher in females than males, with similar kinetic profiles. Compared to previous results in males, ibogaine showed sex specific effect at the level of antioxidant cellular system. Effects of ibogaine in rats are sex- and tissue-specific, and also dose- and time-dependent.
