» Articles » PMID: 35625734

Therapeutic Properties of Ayahuasca Components in Ischemia/Reperfusion Injury of the Eye

Overview
Journal Biomedicines
Date 2022 May 28
PMID 35625734
Authors
Affiliations
Soon will be listed here.
Abstract

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.

Citing Articles

From Nature to Treatment: The Impact of Pterostilbene on Mitigating Retinal Ischemia-Reperfusion Damage by Reducing Oxidative Stress, Inflammation, and Apoptosis.

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.


Electroretinographical Analysis of the Effect of BGP-15 in Eyedrops for Compensating Global Ischemia-Reperfusion in the Eyes of Sprague Dawley Rats.

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.

References
1.
Nichols D . N,N-dimethyltryptamine and the pineal gland: Separating fact from myth. J Psychopharmacol. 2017; 32(1):30-36. DOI: 10.1177/0269881117736919. View

2.
Chouchani E, Pell V, Gaude E, Aksentijevic D, Sundier S, Robb E . Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature. 2014; 515(7527):431-435. PMC: 4255242. DOI: 10.1038/nature13909. View

3.
Manni M, Rigacci S, Borchi E, Bargelli V, Miceli C, Giordano C . Monoamine Oxidase Is Overactivated in Left and Right Ventricles from Ischemic Hearts: An Intriguing Therapeutic Target. Oxid Med Cell Longev. 2017; 2016:4375418. PMC: 5156804. DOI: 10.1155/2016/4375418. View

4.
Bergeron R, Debonnel G . Effects of low and high doses of selective sigma ligands: further evidence suggesting the existence of different subtypes of sigma receptors. Psychopharmacology (Berl). 1997; 129(3):215-24. DOI: 10.1007/s002130050183. View

5.
Liu S, Luo W, Wang Y . Emerging role of PARP-1 and PARthanatos in ischemic stroke. J Neurochem. 2021; 160(1):74-87. PMC: 9010225. DOI: 10.1111/jnc.15464. View