This rodent study investigates the effects of administering DMT in renal ischemia-reperfusion (I/R) injury (robust inflammatory and oxidative stress response to hypoxia and reperfusion which disturbs the organ function) and its hematological (blood-related) and metabolic consequences. It found that DMT could diminish but cannot completely prevent the impairment post the renal I/R.
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 c. 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.”
Authors: Katalin Peto, Norbert Nemeth, Anita Mester, Zsuzsanna Magyar, Souleiman Ghanem, Viktoria Somogyi, Bence Tanczos, Adam Deak, Laszlo Bidig, Ede Frecska & Balazs Nemes
Summary
consequences of renal ischemia-reperfusion and their modulation by N,N-dimethyltryptamine on a rat model Katalin Petoa , Norbert Nemetha,∗, Anita Mestera , Zsuzsanna Magyara , Souleiman Ghanema , Viktoria Somogyia , Bence Tanczosa , Adam Deaka , Laszlo Bidigab, Ede Frecskac,1 and Balazs Nemesd,1 a Department of Operative Techniques and Surgical Research, Institute of Surgery,
Renal ischemia-reperfusion injury may occur in a broad spectrum of clinical settings including surgery, trauma, dehydration or sepsis. Many factors are involved in the pathophysiology of the ischemia-reperfusion injury.
Ischemia-reperfusion injury causes tissue damage due to a decrease in oxidative metabolism, accumulation of waste products and depletion of ATP, and further damage occurs during the subsequent reperfusion. These mechanisms contribute to early graft rejection and to the remote injury of other organs.
In 2014 Szabo et al. demonstrated that DMT has an immune-modulator potential through the sigma-1 receptor of human immune cells, and that this effect may contribute to tissue regeneration. In our study we hypothesized that administration of DMT can be protective against I/R-induced alterations.
Left femoral artery was cannulated for blood samplings, both kidneys were gently clamped, and a 120-minute reperfusion period followed. In the treated group, DMT was administered 15 minutes before ligating/clamping the renal vessels, and again 60 minutes later.
Blood samples were taken from the cannulated artery before the ischemia, just after clip removal, at the 30th, 60th, and 120th minute of reperfusion, and at for histological examinations.
Hematological parameters, glucose and electrolytes were determined, and red blood cell deformability was determined by LoRRca MaxSis Osmoscan rotational ektacytometer. The elongation index values were determined in the function of sheer stress (Pa), and the maximal elongation index and the shear stress at half EImax were calculated. Red blood cell aggregation was tested by a Myrenne MA-1 erythrocyte aggregometer, based on light-transmittance method. Higher aggregation index values reflect enhanced aggregation.
Total white blood cell count and platelet count were stable in Control group, but slightly increased in I/R group and moderately decreased in I/R+DMT group after reperfusion. Blood pH decreased in Control group and more in I/R group by the end of the experiment.
Blood lactate concentration increased in parallel to pH in all groups, but the largest rise was found in I/R group. The glucose concentration decreased in all groups, but the most expressed decrease was found in I/R+DMT group. The elongation index and the shear stress of red blood cells were measured. The values were lower in the I/R group than in the Control group at the end of the bilateral renal ischemia.
The relative values of the lipids in the blood rose by the end of the ischemic period and were elevated in the I/R group and the I/R+DMT group. The values of M1 5 s have changed by time both in the I/R and the I/R+DMT groups. The values in the I/R+DMT group started later and showed a peak at R-30. The M 10 s values decreased in the Control groups, reaching significant level by the 60th minute of the reperfusion, and increased in the I/R group at I-60 and at R-30 time points. The I/R+DMT group showed a peak at R-30 time point.
Transplantation is the only definitive treatment for patients with end stage kidney disease. Ischemia reperfusion injury may occur at various stages of transplantation, and may influence the micro-rheological parameters such as red blood cell aggregation and deformability.
Red blood cells’ membrane, structural proteins and haemoglobin molecule are affected by oxidative stress, inflammation and acute phase reactions in ischemia-reperfusion injury, which results in worsened micro-rheological parameters.
There are only few data about hemorheological changes in kidney ischemia-reperfusion in contrast to other organs such as heart, lungs, liver and bowels. However, improving hemorheological parameters can reduce the ischemia-reperfusion injury in the graft.
Several agents have been demonstrated to protect against I/R injury having anti-inflammatory properties through various pathways. DMT, a bioactive ingredient of the Chinese medicinal herb, Thunder God Vine, was found to reduce the damage caused by I/R concerning the alterations in the micro-rheological changes. The findings on red blood cell aggregation are controversial. The process might have been altered by the light-transmission techniques.
We found that metabolic and micro-rheological parameters impair after 60 minutes of renal ischemia and reperfusion. N,N-dimethyl-tryptamine DMT could reduce but not completely prevent the changes in lactate, pH, electrolytes, red blood cell deformability and aggregation.