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

Author(s):Show less -

Mello-Andrade, Francyelli ^[1] ; Cardoso, Clever Gomes ^[2] ; Ribeiro e Silva, Carolina ^[3] ; Chen-Chen, Lee ^[3] ; de Melo-Reis, Paulo Roberto ^[4] ; de Lima, Aliny Pereira ^[1] ; Oliveira, Rhaul ^[5] ; Machado Ferraz, Irvin Bryan ^[5] ; Grisolia, Cesar Koppe ^[5] ; Pinheiro Almeida, Marcio Aurelio ^[6] ; Batista, Alzir Azevedo ^[7] ; Silveira-Lacerda, Elisangela de Paula ^[1]

Affiliation

^[1] Univ Fed Goias, Lab Mol Genet & Cytogenet, Inst Biol Sci, BR-74690900 Goiania, Go - Brazil

^[2] Univ Fed Goias, Dept Morphol, Inst Biol Sci, BR-74690900 Goiania, Go - Brazil

^[3] Univ Fed Goias, Lab Radiobiol & Mutagenesis, Inst Biol Sci, BR-74690900 Goiania, Go - Brazil

^[4] Pontifical Catholic Univ Goias, Lab Expt & Biotechnol Res, Masters Program Environm Sci & Hlth, Sch Med Sci Pharmaceut & Biomed, BR-74605010 Goiania, Go - Brazil

^[5] Univ Brasilia, Lab Toxicol Genet, Dept Genet & Morphol, Inst Biol Sci, BR-70910900 Brasilia, DF - Brazil

^[6] Univ Fed Maranhao, Coordinat Sci & Technol, BR-65080805 Sao Luis, MA - Brazil

^[7] Univ Fed Sao Carlos, Dept Chem, BR-13565905 Sao Carlos, SP - Brazil

• Document type: Journal article
• Source: BIOMEDICINE & PHARMACOTHERAPY; v. 107, p. 1082-1092, NOV 2018.
• Web of Science Citations: 5

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)]PF6 (RuMet) and {[}Ru(LTrp)(bipy)(dppb)]PF6 (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. (AU)

• FAPESP's process: 14/10516-7 - Search for ruthenium (II) complexes, with chemotherapeutic properties: evaluation of possible sinergistic effects and possible action mechanism
• Grantee: Alzir Azevedo Batista
• Support Opportunities: Regular Research Grants