Therapeutic Properties of Ayahuasca Components in Ischemia/Reperfusion Injury of the Eye
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Ischemic eye diseases are major causes of vision impairment. Thus, potential retinoprotective effects of N'N-dimethyltryptamine (DMT) were investigated. To inhibit its rapid breakdown by monoamine-oxidase A (MAO-A) enzyme, DMT was co-administered with harmaline, a β-carboline in the Amazonian Ayahuasca brew. Using ligation, 60 min of ischemia was provoked in eyes of rats, followed by 7 days of reperfusion whilst animals received harmaline alone, DMT + harmaline, or vehicle treatment. After 1 week of reperfusion, electroretinographical (ERG) measurements, histological analysis, and Western blot were performed. Harmaline alone exhibited retinoprotection in ischemia-reperfusion (I/R) which was, surprisingly, counterbalanced by DMT in case of co-administration. As both MAO-A inhibition and DMT increase serotoninergic tone synergistically, communicated to be anti-ischemic, thus, involvement of other pathways was investigated. Based on our experiments, DMT and harmaline exert opposite effects on important ocular proteins such as PARP1, NFκB, MMP9, or HSP70, each having a critical role in a different mechanism of eye-ischemia-related pathologies, e.g., cell death, inflammation, tissue destruction, and oxidative stress. Since DMT is proclaimed to be a promising drug candidate, its potentially undesirable effect on eye-ischemia should be further investigated. Meanwhile, this experiment revealed the potential therapeutic effect of MAO-A inhibitor harmaline in I/R-related eye diseases.
Pelles-Tasko B, Szekeres R, Takacs B, Szilagyi A, Ujvarosy D, Bombicz M Life (Basel). 2024; 14(9).
PMID: 39337931 PMC: 11433448. DOI: 10.3390/life14091148.
Takacs B, Szilagyi A, Priksz D, Bombicz M, Szabo A, Pelles-Tasko B Biomedicines. 2024; 12(3).
PMID: 38540250 PMC: 10967851. DOI: 10.3390/biomedicines12030637.