Functional Parameters of Physiological Systems of Laboratory Primates after Administration of Doxorubicin and Transplantation of Mesenchymal Stem Cells

Bull Exp Biol Med. 2018 May;165(1):115-120. doi: 10.1007/s10517-018-4111-0. Epub 2018 May 24.

Abstract

We studied physiological parameters of rhesus monkeys after administration of anthracycline antibiotic doxorubicin. Intravenous administration of the drug caused intoxication manifested in in an abrupt body weight loss, baldness, vomiting, and exicosis. Intoxication in monkeys determined by the damaging effects of doxorubicin on organs and tissues is also characterized by significant changes in the blood: leukopenia, thrombocytopenia, neutropenia, monocytopenia, lymphocytosis, and a sharp drop of CD20+ B cell content. The total protein and albumin content in the blood significantly decreased. A sharp increase in C-reactive protein was also accompanied by an increase in activity of proinflammatory cytokine IL-6. Transplantation of mesenchymal stem cells in some cases can significantly alleviate doxorubicin-induced damage to organs and maintain normal clinical status of monkeys after two injections of the drug. Late transplantation of stem cells does not have a protective effect and does not protect the animals from the damaging effects of doxorubicin. We found that the protective effect of mesenchymal stem cells depends on the dose of the drug, total number of cells, and the time of their transplantation. It should be noted that human and monkey mesenchymal stem cells produce similar regenerative effects, at least in the doxorubicin toxicity model.

Keywords: doxorubicin; mesenchymal stem cells; primates.

MeSH terms

  • Alopecia / chemically induced
  • Animals
  • Antibiotics, Antineoplastic / toxicity*
  • Body Weight / drug effects
  • C-Reactive Protein / metabolism
  • Doxorubicin / toxicity*
  • Humans
  • Interleukin-6 / metabolism
  • Macaca mulatta
  • Male
  • Mesenchymal Stem Cell Transplantation / adverse effects*

Substances

  • Antibiotics, Antineoplastic
  • Interleukin-6
  • Doxorubicin
  • C-Reactive Protein