Acute toxic effects of ruthenium (II)/amino acid/diphosphine complexes on Swiss mice and zebrafish embryos.

Autor: Mello-Andrade F; Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, 74690-900, Brazil., Cardoso CG; Department of Morphology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, 74690-900, Brazil., Silva CRE; Laboratory of Radiobiology and Mutagenesis, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO,74690-900, Brazil., Chen-Chen L; Laboratory of Radiobiology and Mutagenesis, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO,74690-900, Brazil., Melo-Reis PR; Laboratory of Experimental and Biotechnological Research, Master's Program in Environmental Sciences and Health of School of Medical Sciences, Pharmaceutical and Biomedical, Laboratory, Pontifical Catholic University of Goiás, Goiânia, GO, 74605-010, Brazil., Lima AP; Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, 74690-900, Brazil., Oliveira R; Laboratory of Toxicological Genetics, Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasilia, Brasília, DF, 70910-900, Brazil., Ferraz IBM; Laboratory of Toxicological Genetics, Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasilia, Brasília, DF, 70910-900, Brazil., Grisolia CK; Laboratory of Toxicological Genetics, Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasilia, Brasília, DF, 70910-900, Brazil., Almeida MAP; Coordination of Science and Technology, Federal University of Maranhão, São Luís, MA, 65080-805, Brazil., Batista AA; Department of Chemistry, Federal University of São Carlos, São Carlos, SP, 13565-905, Brazil., Silveira-Lacerda EP; Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, 74690-900, Brazil. Electronic address: silveiralacerda@ufg.br.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2018 Nov; Vol. 107, pp. 1082-1092. Date of Electronic Publication: 2018 Aug 25.
DOI: 10.1016/j.biopha.2018.08.051
Abstrakt: Anticancer potential of ruthenium complexes has been widely investigated, but safety evaluation studies are still scarce. Despite of ruthenium-based anticancer agents are known to cause fewer side effects compared to other metal-based drugs, these compounds are not fully free of toxicity, causing mainly nephrotoxicity. Based on the promising results from antitumor activity of the complexes [Ru(L-Met)(bipy)(dppb)]PF 6 (RuMet) and [Ru(L-Trp)(bipy)(dppb)]PF 6 (RuTrp), for the first time we investigated the toxicity profile of these complexes in rodent and zebrafish models. The acute oral toxicity was evaluated in Swiss mice. The mutagenic and genotoxic potential was determined by a combination of Micronucleus (MN) and Comet assay protocols, after exposure of Swiss mice to RuMet and RuTrp in therapeutic doses. Zebrafish embryos were exposed to these complexes, and their development observed up to 96 h post-fertilization. RuMet and RuTrp complexes showed low acute oral toxicity. Recorded behavioral changes were not recorded, nor were macroscopic morphological changes or structural modifications in the liver and kidneys. These complexes did not cause genetic toxicity, presenting a lack of micronuclei formation and low DNA damage induction in the cells from Swiss mice. In contradiction, cisplatin treatment exhibited high mutagenicity and genotoxicity. RuMet and RuTrp showed low toxicity in the embryo development of zebrafish. The RuMet and RuTrp complexes demonstrated low toxicity in the two study models, an interesting property in preclinical studies for novel anticancer agents.
(Copyright © 2018 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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