Skip to main content

The influence of heterocyclic compound-PAMAM dendrimer complexes on evoked electrical responses in slices of hypoxic brain tissue

Abstract

We used complexes between a fourth generation polyamidoamine (PAMAM) dendrimer and one of two heterocyclic compounds — 1-(6-hydroxyhexyl)-3-(5-phenyl-isoxazole-3-yl)-urea or 5-phenyl-isoxazole-3-carboxylic acid — to reduce oxygen consumption in transverse slices of the hippocampus taken from 4-week old male rats. In vitro electrophysiological experiments revealed that the inhibitory effect of the hypoxic state on the evoked responses was enhanced in the presence of the complexes. The data were analyzed in terms of the potential antitumor effects of these complexes.

Abbreviations

ACSF:

artificial cerebrospinal fluid

EPSP:

excitatory postsynaptic potential

PAMAM:

polyamidoamine

PS:

population spike

References

  1. 1.

    Moen, I. and Stuhr, L.E.B. Hyperbaric oxygen therapy and cancer — a review. Target Oncol. 7 (2012) 233–242.

    PubMed Central  PubMed  Article  Google Scholar 

  2. 2.

    Depret, J., Teboul, J.L., Benoit, G., Mercat, A. and Richard, C. Global energetic failure in brain-dead patients. Transplantation 60 (1995) 966–971.

    CAS  PubMed  Article  Google Scholar 

  3. 3.

    Pastorekova, S., Zatovicova, M. and Pastorek, J. Cancer-associated carbonic anhydrases and their inhibition. Curr. Pharm. Design 14 (2008) 685–698.

    CAS  Article  Google Scholar 

  4. 4.

    Kulchitsky, V.A., Talabaev, M.V., Chernov, A.N., Grigoriev, D.G., Demidchik, Y.E., Shcharbin, D.G., Chekan, N.M., Kazbanov, V.V., Gurinovich, T.A., Gordienko, A.I., Sergeeva, E.K., Potkin, V.I. and Kalunov, V.N. Improving the efficiency of chemotherapeutic drugs by the action on neuroepithelial tumors. In.: Glioma — Exploring Its Biology and Practical Relevance (Anirban Ghosh, Ed.) 21 (2011) 465–486.

    Google Scholar 

  5. 5.

    Kamal, A., Bharathi, E.V., Reddy, J.S., Ramaiah, M.J., Dastagiri, D., Reddy, K., Viswanath, A., Reddy, T.L., Shaik, T.B., Pushpavalli, S.N. and Bhadra, M.P. Synthesis and biological evaluation of 3,5-diaryl isoxazoline/isoxazole linked 2,3-dihydroquinazolinone hybrids as anticancer agents. Eur. J. Med. Chem. 46 (2011) 691–703.

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Cai, X., Hu, J., Xiao, J. and Cheng, Y. Dendrimer and cancer: a patent review (2006-present). Expert Opin. Ther. Pat. 23 (2013) 515–529.

    CAS  PubMed  Article  Google Scholar 

  7. 7.

    Shcharbin, D., Dzmitruk, V., Shakhbazau, A., Goncharova, N., Seviaryn, I., Kosmacheva, S., Potapnev, M., Pedziwiatr-Werbicka, E., Bryszewska, M., Talabaev, M., Chernov, A., Kulchitsky, V., Caminade, A.-M. and Majoral, J.-P. Fourth generation phosphorus-containing dendrimers: prospective drug and gene delivery carriers. Pharmaceutics 3 (2011) 458–473.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  8. 8.

    Ziemba, B., Matuszko, G., Bryszewska, M. and Klajnert, B. Influence of dendrimers on red blood cells. Cell. Mol. Biol. Lett. 17 (2012) 21–35.

    CAS  PubMed  Article  Google Scholar 

  9. 9.

    Lazniewska, J., Milowska, K., Katir, N., El Kadib, A., Bryszewska M., Majoral, J.-P. and Gabryelak, T. Viologen-phosphorus dendrimers exhibit minor toxicity against a murine neuroblastoma cell line. Cell. Mol. Biol. Lett. 18 (2013) 459–478.

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Kulchitsky, V.A., Potkin, V.I., Zubenko, Yu.S., Chernov, A.N., Talabaev, M.V., Demidchik, Y.E., Petkevich, S.K., Kazbanov, V.V., Gurinovich, T.A., Roeva, M.O., Grigoriev, D.G., Kletskov, A.V. and Kalunov, V.N. Cytotoxic effects of chemotherapeutic drugs and heterocyclic compounds at application on the cells of primary culture of neuroepithelium tumors. Med. Chem. 8 (2012) 22–32.

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    Garkun, Y.S., Yakubovich, N.V., Denisov, A.A., Molchanov, P.G., Emel’janova, A.A., Pashkevich, S.G. and Kulchitsky, V.A. Generation of excitatory postsynaptic potentials in the hippocampus after functional modification of glycosaminoglycans. Bull. Exp. Biol. Med. 145 (2008) 395–397.

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Tabata, Y. Nanomaterials of drug delivery systems for tissue regeneration. Meth. Mol. Biol. 300 (2005) 81–100.

    CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Dzmitry Shcharbin.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Potkin, V.I., Shcharbin, D., Denisov, A.A. et al. The influence of heterocyclic compound-PAMAM dendrimer complexes on evoked electrical responses in slices of hypoxic brain tissue. Cell Mol Biol Lett 19, 243–248 (2014). https://doi.org/10.2478/s11658-014-0193-5

Download citation

Keywords

  • Hypoxia
  • Dendrimer
  • Brain slices
  • Postsynaptic potential
  • Antitumor effects
  • Heterocycles
  • Isoxazoles