Ibogaine Has Sex-Specific Plasma Bioavailability, Histopathological and Redox/Antioxidant Effects in Rat Liver and Kidneys: A Study on Females.

Nikola Tatalović,Gordana Koželj,Aleksandra Nikolić-Kokić,Teodora Vidonja Uzelac,Mara Bresjanac,Zorana Oreščanin Dušić,Milica Mijović,Duško Blagojević

doi:10.3390/life12010016

Nikola Tatalović, Gordana Koželj + Show 6 more

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https://doi.org/10.3390/life12010016

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Abstract

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.

Highlights

We examined the effects of ibogaine on erythrocytes, liver and kidneys of female Wistar rats in vivo, 6 and 24 h after treatment with a single oral dose (1 or 20 mg/kg b.w.) in order to compare these results with those obtained in males
Noribogaine was detected after 6 h in all treated animals, but after 24 h in only one
Detected concentration of both ibogaine and noribogaine were higher after higher dose intake, and detected concentrations of noribogaine were higher than ibogaine at all experimental points

Summary

Introduction

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. Compared to previous results in males, ibogaine showed sex specific effect at the level of antioxidant cellular system. 20 mg/kg b.w., i.p.) after 24 and 72 h [13], results suggest species-, tissue- and time-specific ibogaine effects.

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