Immunology & InflammationDMT

Hemorheological and metabolic consequences of renal ischemia-reperfusion and their modulation by N,N-dimethyl-tryptamine on a rat model

Renal ischaemia–reperfusion in rats causes metabolic disturbance (raised lactate, acidosis) and adverse micro-rheological changes (increased erythrocyte aggregation, reduced deformability). Pre‑treatment with the sigma‑1 receptor agonist N,N‑dimethyltryptamine attenuated but did not fully prevent these metabolic and micro‑rheological alterations.

Authors

  • Ede Ottó Frecska

Published

Clinical Hemorheology and Microcirculation
individual Study

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.

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Research Summary of 'Hemorheological and metabolic consequences of renal ischemia-reperfusion and their modulation by N,N-dimethyl-tryptamine on a rat model'

Introduction

Renal ischemia-reperfusion (I/R) involves interruption and restoration of blood flow and oxygenation, producing morphological and functional injury that depends on the duration of ischaemia and circumstances of reperfusion. It is relevant to many clinical contexts, notably transplantation where warm and cold ischaemia occur and reperfusion contributes to acute kidney injury, delayed graft function and chronic graft dysfunction. Previous research implicates metabolic disturbance, reactive oxygen species and inflammation in injury evolution; however, the micro-rheological consequences for red blood cells — specifically deformability and aggregation — have been incompletely characterised in renal I/R. Peto and colleagues set out to determine whether a 60-minute bilateral renal ischaemia followed by unilateral reperfusion alters metabolic and micro-rheological parameters in rats, and whether N,N-dimethyl-tryptamine (DMT), a sigma-1 receptor agonist with reported immunomodulatory and anti-inflammatory activity, can attenuate those changes. The study tested the hypothesis that DMT administration before ischaemia and before reperfusion would reduce I/R-induced deterioration in metabolic markers (for example lactate and acid-base balance) and in erythrocyte deformability and aggregation.

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Study Details

  • Study Type
    individual
  • Journal
  • Compound
  • Topic
  • Author
  • APA Citation

    Peto, K., Nemeth, N., Mester, A., Magyar, Z., Ghanem, S., Somogyi, V., Tanczos, B., Deak, A., Bidiga, L., Frecska, E., & 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, 70(1), 107-117. https://doi.org/10.3233/ch-170361

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