التفاصيل البيبلوغرافية
| العنوان: |
Acute toxic effects of ruthenium (II)/amino acid/diphosphine complexes on Swiss mice and zebrafish embryos. |
| المؤلفون: |
Mello-Andrade, Francyelli1, Lima, Aliny Pereira de1, Silveira-Lacerda, Elisângela de Paula1, Cardoso, Cléver Gomes2, Silva, Carolina Ribeiro e3, Chen-Chen, Lee3, Melo-Reis, Paulo Roberto de4, Oliveira, Rhaul5, Ferraz, Irvin Bryan Machado5, Grisolia, Cesar Koppe5, Almeida, Márcio Aurélio Pinheiro6, Batista, Alzir Azevedo7 |
| المصدر: |
Biomedicine & Pharmacotherapy. Nov2018, Vol. 107, p1082-1092. 11p. |
| مصطلحات موضوعية: |
*RUTHENIUM, *AMINO acids, *DIPHOSPHINE, *LOGPERCH, *FISH embryos, *MAMMALIAN embryos |
| مستخلص: |
Highlights • Preclinical toxicology study of Ru(II)/amino acids/diphosphine complexes. • These complexes are very well tolerated in animal models. • Cisplatin causes genetic toxicity, but not Ru(II)/amino acids/diphosphine complexes. Abstract 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. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
Academic Search Index |
