[Comparison of pharmacological renal preconditioning with dalargin and lithium ions in the model of gentamycin-induced acute renal failure]

Anesteziol Reanimatol. 2015 Jan-Feb;60(1):58-63.
[Article in Russian]

Abstract

Purpose: To examine the efficacy of renal preconditioning effect of dalargin and lithium ions by observing the model of gentamycin-induced acute renalfailure.

Materials and methods: The experiments were performed on white rats, male. The influence of dalargin and lithium ions on the development of gentamycin-induced acute renalfailure was studied in vivo. On the first 24 hours after dalargin injections were terminated, the rats were euthanized humanly. After this we took the blood for a biochemistry study and a renal culture for biochemical test and also for the test of gsk-3β activity. Concentrations of creatinine and urea were studied in serum. The culture samples of renal tubular epithelium before insertion of gentamycin were incubated in dalargin or lithium ions in different concentrations. After that the substratum was immediately changed to gentamycin in different concentrations also and the incubated for 24 hours. After all the standards MTT-test was performed (based on the ability of living cells to reduce the unpainted form by 3-4,5-dimethylthiazol-2-yl-2,5-difenilterarazola to blue crystalline farmazan).

Results: Lithium precondition leads to the 250% increase of gsk-3β concentration (p = 0.035). The same results were observed after injection of dalargin in 50 mcg/kg concentration. Concentration of creatinine was 44% lower in the dalargin group than in the control group (p = 0.022). Concentration of creatinine was 32% lower in the lithium group than in the control group (p = 0.030). Concentration of urea was 27% lower in the lithium group than in the control group (p = 0.049). Morphological inflammatory changes in the control group were more significant also. In vitro studies showed the maximum efficacy in the lithium group. The most effective dalargin concentration was 5 mg/ml.

Conclusion: Lithium and dalargine preconditioning lowers the signs of gentamycine induced acute renal failure and damage rate of renal parenchyma in vivo and in vitro.

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / enzymology
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Cells, Cultured
  • Disease Models, Animal
  • Enkephalin, Leucine-2-Alanine / administration & dosage
  • Enkephalin, Leucine-2-Alanine / analogs & derivatives*
  • Enkephalin, Leucine-2-Alanine / therapeutic use
  • Gentamicins / pharmacology*
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Ischemia / complications
  • Ischemia / enzymology
  • Ischemia / pathology
  • Ischemia / prevention & control*
  • Ischemic Preconditioning / methods*
  • Kidney / blood supply*
  • Kidney / drug effects
  • Kidney / enzymology
  • Kidney / pathology
  • Kidney Function Tests
  • Lithium Chloride / administration & dosage
  • Lithium Chloride / therapeutic use*
  • Male
  • Mitochondria / drug effects
  • Mitochondria / enzymology
  • Phosphorylation
  • Rats

Substances

  • Gentamicins
  • Enkephalin, Leucine-2-Alanine
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, rat
  • Glycogen Synthase Kinase 3
  • Lithium Chloride
  • enkephalin-Leu, Ala(2)-Arg(6)-