RESUMO
Paclitaxel (single intravenous injection in a maximum tolerated dose of 4.6 mg/kg) to white outbred rats causes bone marrow hypoplasia, increased granulocyte and erythroid cell mitosis (metaphase-anaphase transition), and moderate pancytopenia developments in peripheral blood (hypoplastic anemia, deep, short-term neutropenia, lymphopenia and thrombocytopenia) in the first hours after injection. A considerable increase of polyploidy (4n) cells and a moderate increase in the structural changes (chromatid deletions) of chromosomes was observed on bone marrow metaphase plates in 24 h. The drug introduction causes earlier increase in the rate of thymus cells mitosis, a growth in the number of thymocytes with apoptosis signs, and a moderate decrease in the thymus and spleen weight. All changes are reversible. Long-term (90 days after injection) observation revealed decreased lymphocyte count in the peripheral blood and bone marrow and earlier thymus involution.
Assuntos
Antineoplásicos Fitogênicos/toxicidade , Células Progenitoras Mieloides/efeitos dos fármacos , Paclitaxel/toxicidade , Animais , Medula Óssea/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos CBA , Células Progenitoras Mieloides/citologia , Poliploidia , Ratos , Ratos Endogâmicos , Timo/efeitos dos fármacosRESUMO
The effects of administration of the parent substance of high-molecular-weight poly(ethylene oxide) (HMWPEO) with a molecular mass of 3-6 x 10(6) D and the related drug polyetox (representing a water-soluble lyophilized form of HMWPEO suitable for intravenous injection) on the characteristics of peripheral blood and bone marrow were studied in rats. HMWPEO was injected intravenously and intraperitoneally in a single toxic dose. Polyetox was injected intraperitoneally in a therapeutic dose and in 3- and 10-fold doses over a period of 30 days. Single i.v. and i.p. injections of HMWPEO in the maximum tolerable dose leads to a dose-dependent reversible hemolytic anemia of medium degree, neutrophilic leukocytosis, lymphopenia, and thrombocytopenia. The chronic i.p. adminstration of polyetox in a 10-fold therapeutic dose caused red blood cell lysis and led to the development of reversible regenerative anemia.