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Int. J. Mol. Sci. 2018, 19(8), 2370; https://doi.org/10.3390/ijms19082370

The Efficacy of Amifostine against Multiple-Dose Doxorubicin-Induced Toxicity in Rats

1
Department of Experimental Toxicology and Pharmacology, National Poison Control Centre, Military Medical Academy, 11 Crnotravska St, 11000 Belgrade, Serbia
2
Medical Faculty of the Military Medical Academy, University of Defense in Belgrade, 1 Pavla Jurišića-Šturma St, 11000 Belgrade, Serbia
3
Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanského 62, 50003 Hradec Králové, Czech Republic
4
Centre for Clinical Pharmacology, Military Medical Academy, 11 Crnotravska St, 11000 Belgrade, Serbia
5
Institute for Pathology, Military Medical Academy, 11 Crnotravska St, 11000 Belgrade, Serbia
6
Institute for Scientific Information, University of Defense in Belgrade, 1 Pavla Jurišića-Šturma St, 11000 Belgrade, Serbia
7
Department of Neurology, Charles University in Prague, Faculty of Medicine in Hradec Kralove and University Hospital, Simkova 870, 50003 Hradec Králové, Czech Republic
*
Author to whom correspondence should be addressed.
Received: 30 June 2018 / Revised: 4 August 2018 / Accepted: 7 August 2018 / Published: 12 August 2018
(This article belongs to the Special Issue Frontiers in Drug Toxicity Prediction)
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Abstract

Amifostine is well known cytoprotector which is efficient when administered before a wide range of antineoplastic agents. The aim of our study was to investigate amifostine effects on doxorubicin-induced toxic changes in rats. Amifostine (75 mg/kg ip) was given 30 min before each dose of doxorubicin (cumulatively 20 mg/kg ip, for 28 days). The animals’ whole-body, liver, and kidney weight, serum biochemical examination, as well as microscopic examination of bone marrow, peripheral blood, liver, and kidney, were done on day 56 of the study. Hepatic and renal alterations were carefully quantified by semiquantitative grading scales—hepatic and renal damage score, respectively. In amifostine-pretreated rats, the number of peripheral blood leukocytes was significantly higher in comparison to doxorubicin-only treated group, preferentially protecting neutrophils. In the same group of rats, hepatic and renal alterations associated with polymorphonuclear cell infiltrates were significantly less severe than those observed in animals receiving only doxorubicin. Our results showed that amifostine successfully protected rats against multiple-dose doxorubicin-induced toxicity by complex, and still not fully elucidated mechanisms of action. View Full-Text
Keywords: doxorubicin; amifostine; bone marrow; hepatotoxicity; nephrotoxicity; rats doxorubicin; amifostine; bone marrow; hepatotoxicity; nephrotoxicity; rats
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Jaćević, V.; Dragojević-Simić, V.; Tatomirović, Ž.; Dobrić, S.; Bokonjić, D.; Kovačević, A.; Nepovimova, E.; Vališ, M.; Kuča, K. The Efficacy of Amifostine against Multiple-Dose Doxorubicin-Induced Toxicity in Rats. Int. J. Mol. Sci. 2018, 19, 2370.

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