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.
Highlights
Doxorubicin (DOX) is an anthracycline antibiotic that is used as an antineoplastic agent in hematological, as well as in solid malignancies, due to its high antitumor efficacy [1,2,3,4,5,6,7]
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
Summary
Doxorubicin (DOX) is an anthracycline antibiotic that is used as an antineoplastic agent in hematological, as well as in solid malignancies, due to its high antitumor efficacy [1,2,3,4,5,6,7]. It is well known that DOX is able to interfere with a number of biochemical functions within cells, but the precise molecular pathogenesis of both therapeutic and toxic effects are still controversial [4,5]. There are numerous experimental models concerning these subjects, which showed DOX-induced bone marrow toxicity, cardiotoxicity, hepatotoxicity, nephrotoxicity, and toxic effects on the GI tract (GIT), reproductive system, and nervous system [4,9,10,11,12,13,14,15]. DOX acts as a strong inhibitor of DNA duplication and transcription, with the most obvious consequences on tissues with strong proliferative potential, such as bone marrow, GIT, and the reproductive system. Oxidative stress, apoptosis, and inflammation can be taken as possible mechanisms of DOX multiple-organ toxicity, such as cardiotoxicity on the first place [5,12,15,16,17,18,19]
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