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

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 (SOD1 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.

Ex Vivo Effect of Ibogaine on the Transcriptional Level of Antioxidant Defense Related Genes in Honey Bee (Apis mellifera, L.) Midgut

“…But, paraquat itself is superoxide generating agent comparing to ibogaine that influence cellular energetic leads toward superoxide imbalance. Ibogaine glycogenolytic activity as well as elevation of SOD1 activity was also shown in different rat tissues [21,22] suggesting some common cellular metabolic ibogaine mechanism(s) of action, but with different time scale and intensity that are species and tissue specific.…”

Ibogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and KATP Channels Mediated

“…In a single dose, ibogaine stimulated utilization and releasing of ATP right after addition and increases its re-synthesis, oxidative metabolism and respiration followed by the increase of cellular reactive oxygen species [ 12 , 13 ]. Treatment with single oral dose of ibogaine in vivo showed higher glycogenolytic and mitochondrial activity accompanied by increased hepatic xanthine oxidase activity suggesting faster adenosine turnover [ 6 , 7 ]. Therefore, increased contractile activity observed in spontaneously active uteri found in our experiment can be a manifestation of the redirection of ATP consumption after ibogaine addition, since ATP is an internal excitatory transmitter [ 38 ] that induces muscular contraction coupled to differential signal pathways leading to intracellular Ca 2+ increase and mobilization [ 15 ].…”

“…However, in our previous experiments on rats treated with per os doses (1 and 20 mg/b.w.) that affected its energetic metabolism and redox balance, no serious toxic and harmful ibogaine effects were shown [ 6 , 7 ]. Here, in parallel, we aimed to explore the mechanisms of its action on ex vivo model that combined ibogaine pharmacological, metabolic, and redox properties.…”