RESUMO
Breast cancer is one of the most prevalent cancer types among women. The use of magnetic fluids for specific delivery of drugs represents an attractive platform for chemotherapy. In our previous studies, it was demonstrated that maghemite nanoparticles coated with rhodium (II) citrate (Magh-Rh2Cit) induced in vitro cytotoxicity and in vivo antitumor activity, followed by intratumoral administration in breast carcinoma cells. In this study, our aim was to follow intravenous treatment to evaluate the systemic antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Female Balb/c mice were evaluated with regard to toxicity of intravenous treatments through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine and liver, kidney, and lung histology. The antitumor activity of rhodium (II) citrate (Rh2Cit), Magh-Rh2Cit, and maghemite nanoparticles coated with citrate (Magh-Cit), used as control, was evaluated by tumor volume reduction, histology, and morphometric analysis. Magh-Rh2Cit and Magh-Cit promoted a significant decrease in tumor area, and no experimental groups presented hematotoxic effects or increased levels of serum ALT and creatinine. This observation was corroborated by the histopathological examination of the liver and kidney of mice. Furthermore, the presence of nanoparticles was verified in lung tissue with no morphological changes, supporting the idea that our nanoformulations did not induce toxicity effects. No studies about the systemic action of rhodium (II) citrate-loaded maghemite nanoparticles have been carried out, making this report a suitable starting point for exploring the therapeutic potential of these compounds in treating breast cancer.
Assuntos
Antineoplásicos/farmacologia , Compostos Férricos/farmacologia , Neoplasias Mamárias Experimentais/tratamento farmacológico , Ródio/farmacologia , Alanina Transaminase/sangue , Animais , Feminino , Compostos Férricos/toxicidade , Hepatócitos/patologia , Rim/fisiopatologia , Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Experimentais/mortalidade , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas , Ródio/toxicidade , Taxa de SobrevidaRESUMO
Rhodium(II) carboxylate (acetate, propionate, and butyrate) adducts with isonicotinic acid (Hisonic) were prepared for study. Elemental analyses and electronic spectroscopy show that the adducts contain two isonicotinic acid ligands coordinated in the axial position at the pyridinic nitrogen. The in vitro (K562 human leukemic cell line) assay and LD10 in mice results, in addition to tests of solubility, suggest that, in the presence of blood lipids or cellular membrane, the adducts dissociate into the parent compounds and the rhodium(II) carboxylate enters the cell to carry out its biological effects.
Assuntos
Antineoplásicos/farmacologia , Compostos Organometálicos/farmacologia , Ródio/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/toxicidade , Humanos , Dose Letal Mediana , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Compostos Organometálicos/química , Compostos Organometálicos/toxicidade , Ródio/química , Ródio/toxicidade , Solubilidade , Células Tumorais Cultivadas , ÁguaRESUMO
Rhodium II citrate was tested in mice for acute toxicity, antitumoral activity against Ehrlich ascites carcinoma and inhibition of DNA synthesis by Ehrlich tumor, malignant adrenocortical cells (Y-1) and normal adrenocortical cells (AR-1). At ip doses up to 260 mg/kg, the compound had no toxic effects for up to 14 days. The same total dose given over 4 days significantly increased the survival rate of mice bearing Ehrlich ascites cells. Thymidine incorporation by Ehrlich tumor, Y-1 and AR-1 cells in vitro was inhibited 50% by 0.1 to 0.2 mM concentrations of the compound. We conclude that the increased survival of the tumor-bearing mice was due at least in part to the inhibition of DNA synthesis with a consequent reduction of cell division and tumor growth.
Assuntos
Carcinoma de Ehrlich/patologia , Citratos/farmacologia , DNA/biossíntese , Ródio/farmacologia , Animais , Carcinoma de Ehrlich/mortalidade , Citratos/toxicidade , Camundongos , Ródio/toxicidade , Timidina/metabolismoRESUMO
Rhodium II citrate was tested in mice for acute toxicity, antitumoral activity against Ehrlich ascites carcinoma and inhibition of DNA synthesis by Ehrlich tumor, malignant adrenocortical cells (Y-1) and normal adrenocortical cells (AR-1)_. At ip doses up to 260 mg/Kg, the compound had no toxic effects for up to 14 days. The same total dose given over 4 days significantly increased the survial rat of mice bearing Ehrlich ascites cells. Thymidine incorporation by Ehrlkich tumor, Y-1 cells in vitro was inhibited 50% by a.1 to 0.2 mM concentrations of the compound. We conclude that the increase survival of the tumor-bearing mice was due at least in part to the inhibition of DNA synthesis with a consequet reduction of cell division and tumor growth
Assuntos
Camundongos , Animais , Carcinoma de Ehrlich/patologia , Citratos/farmacologia , Ródio/farmacologia , Carcinoma de Ehrlich/mortalidade , Citratos/toxicidade , DNA/biossíntese , Ródio/toxicidadeRESUMO
o citrato de ródio II sintetizado na procura de complexos de ródio com atividade anti-tumoral e baixa toxicidade. Näo foram observados mortes ou outros sinais de toxicidade após injeçäo de 260 mg/Kg de citrato de ródio II, intra-peritonial em camundongos observados durante 14 dias. A substância provaca um quadro inflamatório que se caracteriza por edema persistente por 24 horas, quando injetada na pata de ratos. Injetada na cavidade peritonial há aumento de neutrófilos segmentados no exudato peritoneal bem como aumento significativo no número de macrófagos espraiados