Efekat ibogaina na sistem antioksidativne zaštite u perifernim tkivima i kontraktilnost terminalnog ileuma kod mužjaka pacova
Effect of ibogaine on antioxidative defense system in peripheral tissues and terminal ileum contractility in male rats
Doctoral thesis (Published version)
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Ibogaine, administered as a single oral dose (1-25 mg/kg body weight, (b.w.)), 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 b.w.) on antioxidative defenses in different rat tissues. 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 antioxidant enzymes in the liver and erythrocytes after ibogaine treatment, regardless of the dose. These results suggest there were no systemic ibogaine effects regarding antioxidant defense. Hepatic xanthine oxidase activity was elevated in rats that received 20 mg/kg compared to the controls, suggesting faster adenosine turnover. TBARS concentration was elevated in the group treated with 1 mg/kg after 24 h compared to the controls, suggesting mild oxidative stress. It was shown that ibogaine in heart after 6 h diminished the amount of protein -SH groups suggesting intra-protein oxidation, which along disturbed energetic homeostasis could lead to discrete cellular oxidative damages and possible heart failure. Ibogaine inhibited ex vivo ileum contractile activity with doses below mM. The effect was stronger in electrically stimulated contractions than tonic. Pretreatment with different potassium channel related agents showed that ibogaine obtained its inhibitory activity partially through KATP channels. Ibogaine induced the elevation of superoxide dismutase (SOD), catalase activity 9 ex vivo, but this effect was diminished by addition of glibenclamide. Ibogaine changed redox homeostasis in testicles as well, and elevated SOD activity suggested the importance of the preservation of delicate balance of superoxide and hydrogen peroxide concentrations that is crucial in sperm capacitation. Our results showed that ibogaine in doses applied in vivo per os influenced redox state and changed antioxidant activity, but response is highly tissue-, dose- and time- specific, without clear common characteristic.