The age factor for mitoxantrone's cardiotoxicity: Multiple doses render the adult mouse heart more susceptible to injury

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Jose Luis Dores Sousa (Author) Other; Jose Alberto Duarte (Author) FADEUP; Vitor Seabra (Author) Other; Maria de Lourdes Bastos (Author) FFUP; Felix Carvalho (Author) FFUP; Vera Marisa Costa (Author) Other

Journal

Title: Toxicology

Vol. 329

Pages: 106-119

ISSN: 0300-483X

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 15 Citations

Scopus - 21 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-00A-78Y

DOI: 10.1016/j.tox.2015.01.006

Abstract (EN): Age is a known susceptibility factor for the cardiotoxicity of several anticancer drugs, including mitoxantrone (MTX). The impact of anticancer drugs in young patients is underestimated, thus we aimed to evaluate the cardiotoxicity of MIX in juvenile and adult animals. Juvenile (3 week-old) and adult (8-10 week-old) male CD-1 mice were used. Each group was treated with a 9.0 mg/kg cumulative dose of MIX or saline; they were maintained in a drug-free period for 3-weeks after the last administration to allow the development of late toxicity (protocol 1), or sacrificed 24 h after the last MIX administration to evaluate early cardiotoxicity (protocol 2). In protocol 1, no adult mice survived, while 2 of the juveniles reached the end of the protocol. High plasma aspartate aminotransferase/alanine aminotransferase ratio and a high cardiac reduced/oxidized glutathione ratio were found in the surviving MIX-treated juvenile mice. In protocol 2, a significant decrease in plasma creatine-kinase MB in juveniles was found 24 h after the last MIX-administration. Cardiac histology showed that both MIX-treated populations had significant damage, although higher in adults. However, MIX-treated juveniles had a significant increase in fibrotic tissue. The MIX-treated adults had higher values of cardiac GSSG and protein carbonylation, but lower cardiac noradrenaline levels. For the first time, mature adult animals were shown to be more susceptible to MIX as evidenced by several biomarkers, while young animals appear to better adjust to the MIX-induced cardiac injury. Even so, the higher level of fibrotic tissue and the histological damage showed that MIX also causes cardiac damage in the juvenile population.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14