OPEN Foundation

K. Peto

N,N-dimethyltryptamine Prevents Renal Ischemia-Reperfusion Injury in a Rat Model

Abstract

BACKGROUND:

Ischemia reperfusion (I/R) injury remains one of the most challenging fields of organ transplantation. It is highly associated with the use of expanded criteria donors that might conclude to delayed graft function or early or late graft failure.

OBJECTIVE:

To investigate the metabolic, microcirculatory parameters, and histologic changes under the effect of N,N-dimethyltryptamine (DMT) in a renal I/R model in rats.

METHOD:

In 26 anesthetized rats both kidneys were exposed. In the control group (n = 6) no other intervention happened. In 20 other animals, the right renal vessels were ligated, and after 60 minutes the right kidney was removed. The left renal vessels were clamped for 60 minutes then released, followed by 120 minutes of reperfusion. In the I/R group (n = 10), there was no additive treatment, while in I/R + DMT group (n = 10) DMT was administered 15 minutes before ischemia. Blood samples were taken, laser Doppler measurement was performed, and both kidneys were evaluated histologically.

RESULTS:

Microcirculation (blood flux units [BFU]) diminished in all groups, but remarkably so in the I/R + DMT group. This group compensated better after the 30th minute of reperfusion. The control and I/R + DMT groups had similar BFUs after 120 minutes of reperfusion, but in the I/R group BFU was higher. Tubular necrosis developed in the I/R and I/R + DMT groups too; it was moderated under DMT effect, and severe without. Histologic injuries were less in I/R + DMT Group compared to non-treated animals.

CONCLUSION:

Histologic changes characteristic to I/R injuries were reversible and microcirculation recovered at the end of 120 minutes reperfusion under the administration of DMT. DMT can be used for renoprotection in kidney transplantation.

Nemes, B., Pető, K., Németh, N., Mester, A., Magyar, Z., Ghanem, S., … & Bidiga, L. (2019, May). N, N-dimethyltryptamine Prevents Renal Ischemia-Reperfusion Injury in a Rat Model. In Transplantation proceedings (Vol. 51, No. 4, pp. 1268-1275). Elsevier. 10.1016/j.transproceed.2019.04.005
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Hemorheological and metabolic consequences of renal ischemia-reperfusion and their modulation by N,N-dimethyl-tryptamine on a rat model

Abstract

BACKGROUND:
Micro-rheological relations of renal ischemia-reperfusion (I/R) have not been completely elucidated yet. Concerning anti-inflammatory agents, it is supposed that sigma-1 receptor agonist N,N-dimethyl-tryptamin (DMT) can be useful to reduce I/R injury.
OBJECTIVE:
To investigate the micro-rheological and metabolic parameters, and the effects of DMT in renal I/R in rats.
METHODS:
In anesthetized rats from median laparotomy both kidneys were exposed. In Control group (n = 6) no other intervention happened. In I/R group (n = 10) the right renal vessels were ligated and after 60 minutes the organ was removed. The left renal vessels were clamped for 60 minutes followed by 120-minute reperfusion. In I/R+DMT group (n = 10) DMT was administered 15 minutes before the ischemia. Blood samples were taken before/after ischemia and during the reperfusion for testing hematological, metabolic parameters, erythrocyte deformability and aggregation.
RESULTS:
Lactate concentration significantly increased and accompanied with decreased blood pH. Enhanced erythrocyte aggregation and impaired deformability were observed from the 30th minute of reperfusion. In I/R+DMT group we found diminished changes compared to the I/R group (lactate, pH, electrolytes, red blood cell deformability and aggregation).
CONCLUSIONS:
Metabolic and micro-rheological parameters impair during renal I/R. DMT could reduce but not completely prevent the changes in this rat model.
Peto, K., Nemeth, N., Mester, A., Magyar, Z., Ghanem, S., Somogyi, V., … & Nemes, B. (2018). Hemorheological and metabolic consequences of renal ischemia-reperfusion and their modulation by N, N-dimethyl-tryptamine on a rat model. Clinical hemorheology and microcirculation, (Preprint), 1-11. 10.3233/CH-170361
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