Aims
To report the acute toxicity of 5-MeO-MiPT in mice, followed by quantitative toxicological analysis of blood and organs, hystotoxicological and immunohistochemical analysis of tissues and cells. Study design: Animal experiment
Background
The hallucinogenic tryptamine analog 5-methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MiPT) causes social problems worldwide. There are several studies on the metabolism; however, not more studies were found in the literature on acute toxicity. Aims: To report the acute toxicity of 5-MeO-MiPT in mice, followed by quantitative toxicological analysis of blood and organs, hystotoxicological and immunohistochemical analysis of tissues and cells. Study design: Animal experiment
Conclusion
Low-dose 5-MeO-MiPT did not cause any serious histopathological effects on the liver, kidney, and brain. High doses induce apoptotic cell death through caspase activity.
Methods
In vivo experiments were performed using CD1 adult female mice (n=26). Animals were caged in 4 groups randomly. First group was a control (n=3). Second group was vehicle control (n=3) and injected 150 μL of blank solution (50% dimethyl sulfoxide in saline /0.9% of NaCl). While for acute toxicity experiments, 5-MeO-MiPT was added to a blank solution in order to obtain a dose of 0.27 mg/kg in 150 μL injection (n=10) and the last group were injected 2.7 mg/kg 5-MeO-MiPT in a 150 μL injection (n=10). Quantitative toxicological analysis, hystotoxicological and immunohistochemical analysis were performed.
Results
In the toxicological analysis, 5-MeO-MiPT was found negative in biological samples which were control, vehicle control, and 0.27 mg/kg dose mice groups. 5-MeO-MiPT was found 2.7-13.4 ng/mL in blood, 11-29 ng/g in kidney, 15.2-108.3 ng/g in liver, and 1.5-40.6 ng/g in the brain in 2,7 mg/kg injected group. In a low dose of the 5-MeO-MiPT liver section, compared with normal tissues, the difference in staining was statistically significant (p<0.0001). In high-dose of 5-MeO-MiPT, H-score showed that the increase in the number of Caspase-3 positive cells was significant compared to the control (p<0.05). In high-dose of 5-MeO-MiPT, intense Caspase-3 immunoreactivity was observed and the increase in the number of Caspase-3 positive cells compared to the control was statistically significant (p<0.05). In brain section, the statistics of the results obtained from the H-score showed that the increase in the number of Caspase-3 positive cells was significant compared to the control (p=0.0183). In vehicle control liver section, there were few Caspase-8 positive cells characterized by a light brown appearance (p=0.0117). In the high-dose 5-MeO-MiPT group, the numbers of positive cells at low and high doses of 5-MeO-MiPT group were statistically significant compared to the control (p<0.05). In the high-dose 5-MeO-MiPT group, Caspase-8 immunoreactivity was detected in the glomerular structures. Compared to control, the increase in Caspase-8 immunoreactivity was found to be statistically significant (p<0.05).