Effects of ibogaine per os application on redox homeostasis in rat liver and erythrocytes

Abstract

Ibogaine, administered as a single oral dose (1-25 mg/kg body weight), has been used as an addiction-interrupting agent. Its effects persist for up to 72 h. Ex vivo results showed that ibogaine induced cellular energy consumption and restitution, followed by increased reactive oxygen species production and antioxidant activity. Therefore, the aim of this work was to explore the effect of a single oral dose of ibogaine (1 or 20 mg/kg body weight) on antioxidative defenses in rat liver and erythrocytes. Six and 24 h after ibogaine administration, histological examination showed glycogenolytic activity in hepatocytes, which was highest after 24 h in animals that received 20 mg/kg ibogaine. There were no changes in the activities of superoxide dismutases, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase in the liver and erythrocytes after ibogaine treatment, regardless of the dose. Hepatic xanthine oxidase activity was elevated in rats that received 20 mg/kg compared to the controls (p<0.01), suggesting faster adenosine turnover. TBARS concentration was elevated in the group treated with 1 mg/kg after 24 h compared to the controls (p<0.01), suggesting mild oxidative stress. Our results show that ibogaine treatment influenced hepatic redox homeostasis, but not sufficiently to remodel antioxidant enzyme activities at 6 and 24 h post-ibogaine application.

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

“…Although ibogaine can act as a pro-antioxidant, promoting increased antioxidant activity in a dose-and time-dependent manner in different in vitro and ex vivo model systems, including yeast [7] and human erythrocytes [8], our recent in vivo findings [6] showed that ibogaine treatment influenced hepatic redox homeostasis, but not to a sufficient extent to remodel antioxidant enzyme activities at 6 and 24 h post ibogaine application. However, in vitro and ex vivo experiments were performed with much higher doses than used in vivo and per os application, where its pro-antioxidant ability in the liver was not as convincing [6]. Results showed that in vivo intragastric application in rats and mice led to much lower ibogaine and noribogaine concentrations in blood plasma [6,12] when compared to doses used in vitro.…”

“…However, in vitro and ex vivo experiments were performed with much higher doses than used in vivo and per os application, where its pro-antioxidant ability in the liver was not as convincing [6]. Results showed that in vivo intragastric application in rats and mice led to much lower ibogaine and noribogaine concentrations in blood plasma [6,12] when compared to doses used in vitro. Therefore, the pro-antioxidant role of ibogaine was questioned.…”

“…per os caused depletion of liver glycogen 6 and 24 h post treatment, suggesting extensive utilization of glucose. In addition, thiobarbituric acid reactive substances (TBARS) were elevated 6 h after application of 1 mg/kg b.w., suggesting a mild prooxidant effect, but the increase was insufficient to promote a systemic change in hepatic antioxidant enzyme activities [6]. Previous in vitro findings showed that ibogaine affected cellular energy metabolism as it leads to the rapid discharge of ATP pools in yeast [7] and erythrocytes [8], which is associated with an increase in the amount of certain metabolic enzymes involved in glycolysis and Krebs cycle [9], reactive oxygen species (ROS) production and increased activities of antioxidative enzymes [10].…”

“…However, in vitro and ex vivo experiments were performed with much higher doses than those applied in vivo (after per os application), where its pro-antioxidant ability was not so convincingly shown. Results revealed that in vivo intragastric application in rats and mice led to much lower concentrations of ibogaine and its main metabolite, noribogaine, in blood plasma as compared to doses used in vitro [6,12].…”

“…In this work, we explored the in vivo effects of ibogaine, using doses already applied in our previous work (1 or 20 mg/kg b.w. per os, the effects of which were examined after 6 and 24 h [6]), on the activities of antioxidative enzymes: cytosolic copper-zinc superoxide dismutase (SOD1), mitochondrial manganese super-oxide dismutase (SOD2), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and glutathione S-transferases (GST), after 6 and 24 h in rat kidney. We also measured the amounts of TBARS and -SH groups as markers of lipid peroxidation and the thiol-based redox state, respectively.…”