Autor(es):
Rossato, Luciana G. 
; Costa, Vera M. ; Dallegrave, Eliane ; Arbo, Marcelo ; Dinis-Oliveira, Ricardo J. ; Santos-Silva, Alice ; Duarte, José A. ; Bastos, Maria de Lourdes ; Palmeira, C. M. ; Remião, Fernando
Data: 2014
Identificador Persistente: http://hdl.handle.net/10316/25490
Origem: Estudo Geral - Universidade de Coimbra
Assunto(s): MULTIPLE-SCLEROSIS; PROTEIN-SYNTHESIS; LIVER; HEPATOTOXICITY; CELLS; TOXICITY; PHARMACOKINETICS; CARDIOTOXICITY; CHEMOTHERAPY; INHIBITION
Descrição
Mitoxantrone (MTX) is an antineoplastic agent that can induce hepato- and haematotoxicity. This work aimed to
investigate the occurrence of cumulative early and late MTX-induced hepatic and haematological disturbances in an vivo model.
A control group and two groups treated with three cycles of 2.5 mg/kg MTX at days 0, 10 and 20 were formed. One of the treated
groups suffered euthanasia on day 22 (MTX22) to evaluate early MTX toxic effects, while the other suffered euthanasia on
day 48 (MTX48), to allow the evaluation of MTX late effects. An early immunosuppression with a drop in the IgG levels was
observed, causing a slight decrease in the plasma total protein content. The early bone marrow depression was followed by signs
of recovery in MTX48. The genotoxic potential of MTX was demonstrated by the presence of several micronuclei in MTX22
leucocytes. Increases in plasma iron and cholesterol levels in the MTX22 rats were observed, while in both groups increases in
the unconjugated bilirubin, C4 complement, and decreases in the triglycerides, alanine aminotransferase, alkaline phosphatase
and transferrin were found in plasma samples. On MTX 48, the liver histology showed more hepatotoxic signs, the hepatic levels
of reduced and oxidized glutathione were increased, and ATP hepatic levels were decreased. However, the hepatic total protein
levels were decreased only in the livers of MTX22 group. Results demonstrated the MTX genotoxic effects, haemato- and direct
hepatotoxicity. While the haematological toxicity is ameliorated with time, the same was not observed in the hepatic injury. This work was supported by the Fundação para a Ciencia e
Tecnologia (FCT) - project (EXPL/DTP-FTO/0290/2012) -
QREN initiative with EU/FEDER financing through COMPETE
- Operational Programme for Competitiveness Factors.
The work was also supported by FCT within the framework
of Strategic Projects for Scientific Research Units of R&D
(project PEst-C/EQB/LA0006/2011). LGR, VMC and RJD-O
thank FCT for their PhD grant (SFRH/BD/63473/2009) and
Post-doc grants (SFRH/BPD/63746/2009) and (SFRH/BPD/
36865/2007), respectively. MDA thanks Capes Foundation
(Brazil) for his PhD Grant (BEX 0593/10-9).
