MELPHALAN-INDUCED CYTOTOXICITY IN THE BONE MARROW OF RATS BY FLOW CYTOMETRY MEASUREMENTS

Background. Bone marrow (BM) that contains hematopoietic cells of various lineages is a sensitive target for a number of cytotoxic agents including chemotherapy drugs. Objective. Flow cytometry (FCM) was chosen to test cytotoxicity in BM of rats, that received melphalan either intravenously (i.v....

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Main Authors: B I. Gerashchenko, I. M. Todor, O. O. Shevchuk, V. G. Nikolaev
Format: Article
Language:English
Published: Ukrmedknyha 2019-03-01
Series:International Journal of Medicine and Medical Research
Subjects:
Online Access:https://ojs.tdmu.edu.ua/index.php/ijmr/article/view/9836
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author B I. Gerashchenko
I. M. Todor
O. O. Shevchuk
V. G. Nikolaev
author_facet B I. Gerashchenko
I. M. Todor
O. O. Shevchuk
V. G. Nikolaev
author_sort B I. Gerashchenko
collection DOAJ
description Background. Bone marrow (BM) that contains hematopoietic cells of various lineages is a sensitive target for a number of cytotoxic agents including chemotherapy drugs. Objective. Flow cytometry (FCM) was chosen to test cytotoxicity in BM of rats, that received melphalan either intravenously (i.v.) or intraperitoneally (i.p.). Methods. One group of rats received melphalan i.v. (3 mg/kg) followed by the BM examination on the 3rd and 7th day after drug administration, whereas another group of animals received this drug i.p. in total doses of 9 and 15 mg/kg followed by the BM examination on the next day after the 3rd and 5th injection of the drug. BM cells were stained with acridine orange and analyzed by FCM. Cytotoxicity was assessed by determining the percentage of total nucleated cells (TNC%) among the whole BM cell population and by determining the percentage of polychromatic erythrocytes (PCE%) among the whole population of enucleated erythrocytes. Results. Regardless of the dose and regimen of melphalan administration, either i.v. or i.p. administered drug caused a significant reduction of TNC%. On the average, the i.p. administered drug resulted in about 2.0-fold decrease of TNC% (P<0.05), while the i.v. administered drug resulted in about 1.3-fold decrease of TNC% (P<0.05). As for enucleated erythrocytes, the i.p. administered drug resulted in about 1.4-fold decrease of PCE% (P<0.05), whereas the i.v. administered drug did not cause any changes in the PCE%. Conclusions. Under these experimental conditions, i.p. administrated melphalan is considerably more cytotoxic than i.v. administered melphalan. This cytotoxic effect is preferentially due to impaired erythropoiesis.
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spelling doaj.art-3c02507a71a34a0ab2ac408cdcfc4db22023-05-02T08:05:41ZengUkrmedknyhaInternational Journal of Medicine and Medical Research2413-60772414-99852019-03-0142727810.11603/ijmmr.2413-6077.2018.2.98369836MELPHALAN-INDUCED CYTOTOXICITY IN THE BONE MARROW OF RATS BY FLOW CYTOMETRY MEASUREMENTSB I. Gerashchenko0I. M. Todor1O. O. Shevchuk2V. G. Nikolaev3R. E. KAVETSKY INSTITUTE OF EXPERIMENTAL PATHOLOGY, ONCOLOGY AND RADIOBIOLOGY, NATIONAL ACADEMY OF SCIENCES OF UKRAINE, KYIV, UKRAINER. E. KAVETSKY INSTITUTE OF EXPERIMENTAL PATHOLOGY, ONCOLOGY AND RADIOBIOLOGY, NATIONAL ACADEMY OF SCIENCES OF UKRAINE, KYIV, UKRAINEI. HORBACHEVSKY TERNOPIL STATE MEDICAL UNIVERSITY, TERNOPIL, UKRAINER. E. KAVETSKY INSTITUTE OF EXPERIMENTAL PATHOLOGY, ONCOLOGY AND RADIOBIOLOGY, NATIONAL ACADEMY OF SCIENCES OF UKRAINE, KYIV, UKRAINEBackground. Bone marrow (BM) that contains hematopoietic cells of various lineages is a sensitive target for a number of cytotoxic agents including chemotherapy drugs. Objective. Flow cytometry (FCM) was chosen to test cytotoxicity in BM of rats, that received melphalan either intravenously (i.v.) or intraperitoneally (i.p.). Methods. One group of rats received melphalan i.v. (3 mg/kg) followed by the BM examination on the 3rd and 7th day after drug administration, whereas another group of animals received this drug i.p. in total doses of 9 and 15 mg/kg followed by the BM examination on the next day after the 3rd and 5th injection of the drug. BM cells were stained with acridine orange and analyzed by FCM. Cytotoxicity was assessed by determining the percentage of total nucleated cells (TNC%) among the whole BM cell population and by determining the percentage of polychromatic erythrocytes (PCE%) among the whole population of enucleated erythrocytes. Results. Regardless of the dose and regimen of melphalan administration, either i.v. or i.p. administered drug caused a significant reduction of TNC%. On the average, the i.p. administered drug resulted in about 2.0-fold decrease of TNC% (P<0.05), while the i.v. administered drug resulted in about 1.3-fold decrease of TNC% (P<0.05). As for enucleated erythrocytes, the i.p. administered drug resulted in about 1.4-fold decrease of PCE% (P<0.05), whereas the i.v. administered drug did not cause any changes in the PCE%. Conclusions. Under these experimental conditions, i.p. administrated melphalan is considerably more cytotoxic than i.v. administered melphalan. This cytotoxic effect is preferentially due to impaired erythropoiesis.https://ojs.tdmu.edu.ua/index.php/ijmr/article/view/9836bone marrowmelphalancytotoxicityflow cytometrypolychromatic erythrocytestotal nucleated cells
spellingShingle B I. Gerashchenko
I. M. Todor
O. O. Shevchuk
V. G. Nikolaev
MELPHALAN-INDUCED CYTOTOXICITY IN THE BONE MARROW OF RATS BY FLOW CYTOMETRY MEASUREMENTS
International Journal of Medicine and Medical Research
bone marrow
melphalan
cytotoxicity
flow cytometry
polychromatic erythrocytes
total nucleated cells
title MELPHALAN-INDUCED CYTOTOXICITY IN THE BONE MARROW OF RATS BY FLOW CYTOMETRY MEASUREMENTS
title_full MELPHALAN-INDUCED CYTOTOXICITY IN THE BONE MARROW OF RATS BY FLOW CYTOMETRY MEASUREMENTS
title_fullStr MELPHALAN-INDUCED CYTOTOXICITY IN THE BONE MARROW OF RATS BY FLOW CYTOMETRY MEASUREMENTS
title_full_unstemmed MELPHALAN-INDUCED CYTOTOXICITY IN THE BONE MARROW OF RATS BY FLOW CYTOMETRY MEASUREMENTS
title_short MELPHALAN-INDUCED CYTOTOXICITY IN THE BONE MARROW OF RATS BY FLOW CYTOMETRY MEASUREMENTS
title_sort melphalan induced cytotoxicity in the bone marrow of rats by flow cytometry measurements
topic bone marrow
melphalan
cytotoxicity
flow cytometry
polychromatic erythrocytes
total nucleated cells
url https://ojs.tdmu.edu.ua/index.php/ijmr/article/view/9836
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