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Cumulative Mitoxantrone‐Induced Haematological and Hepatic Adverse Effects in a Subchronic In vivo Study
Author(s) -
Rossato Luciana G.,
Costa Vera M.,
Dallegrave Eliane,
Arbo Marcelo,
DinisOliveira Ricardo J.,
SantosSilva Alice,
Duarte José A.,
Lourdes Bastos Maria,
Palmeira Carlos,
Remião Fernando
Publication year - 2014
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12143
Subject(s) - in vivo , bilirubin , mitoxantrone , alkaline phosphatase , medicine , toxicity , glutathione , pharmacology , adverse effect , chemistry , chemotherapy , biology , enzyme , biochemistry , microbiology and biotechnology
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 ( MTX 22) to evaluate early MTX toxic effects, while the other suffered euthanasia on day 48 ( MTX 48), to allow the evaluation of MTX late effects. An early immunosuppression with a drop in the I g G 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 MTX 48. The genotoxic potential of MTX was demonstrated by the presence of several micronuclei in MTX 22 leucocytes. Increases in plasma iron and cholesterol levels in the MTX 22 rats were observed, while in both groups increases in the unconjugated bilirubin, C 4 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 MTX 22 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.