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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2013; 59(3): 50-57


Mechanisms of nephrotoxicity of novel anticancer compound maleimide derivative MI-1

Kharchuk IV, Andrukhova OO, Rybal'chenko VK, Andrukhov O

  1. Taras Shevchenko National University, Kyiv, Ukraine
  2. Vienna University of Animal Medicine, Austria
  3. Vienna Medical University, Austria
DOI: https://doi.org/10.15407/fz59.03.050

Abstract

The features of the impact of the maleimide derivative 1-(4-Cl-benzyl)-3-chloro-4-(CF3-fenilamino)-1H-pyrrole-2,5-dione (MI-1) on the viability and apoptosis-induced cell death of renal proximal and distal tubular epithelial cells and the amount of total and phosphorylated ERK1/2 were studied in order to establish possible mechanisms of nephrotoxicity induced by of MI-1. The viability and apoptosis of renal epithelial tubular cells after incubation with MI-1 were perfomed by 3,4,5-dymetyltiazol-2-yl-2,5-diphenyl-tetrazolium bromide (MTT)-test and by flow cytometry after staining with specific antibodies to annexin V, respectively. The amount of ERK 1/2 was determined by Western blotting. The data indicate that MI-1 was more toxic with respect to the epithelial cells of distal than proximal tubule cells. The apoptosis-induced cell death pathway is involved in the mechanisms of MI-1 cytotoxicity. One of the possible mechanisms of MI-1 nephrotoxicity is increase in phosphorylation of ERK1/2 in the distal tubules. At the same time the increase amount of total ERK1/2 in proximal tubules under the influence of MI-1 may contribute to the survival of proximal tubular epithelial cells under the impact of a toxic factor or oxidative stress.

Keywords: Maleimide derivatives, nephrotoxicity, apoptosis, ERK1/2 signalling pathway

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