title: The ruthenium complex cis-(Dichloro)Tetraammineruthenium(III) chloride presents immune stimulatory activity on human peripheral blood mononuclear cells.
abstract: Ruthenium compounds in general are well suited for medicinal applications. They have been investigated as immunosuppressants, nitric oxide scavengers, antimicrobial agents, and antimalarials. The aim of this study is to evaluate the immunomodulatory activity of cis-(dichloro)tetraammineruthenium(III) chloride (cis-[RuCl(2)(NH(3))(4)]Cl) on human peripheral blood mononuclear cells (PBMC). The cytotoxic studies performed here revealed that the ruthenium(III) complex presents a cytotoxic activity towards normal human PBMC, only at very high concentration. Results also showed that cis-[RuCl(2)(NH(3))(4)]Cl presents a dual role on PBMC stimulating proliferation and interleukin-2 (IL-2) production at low concentration and inducing cytotoxicity, inability to proliferate, and inhibiting IL-2 production at high concentration. The noncytotoxic activity of cis-[RuCl(2)(NH(3))(4)]Cl at low concentration towards PBMC, which correlates with the small number of annexin V positive cells and also the absence of DNA fragmentation, suggest that this compound does not induce apoptosis on PBMC. For the first time, we show that, at low concentration (10-100 microg L(-1)), the cis-[RuCl(2)(NH(3))(4)]Cl compound induces peripheral blood lymphocytes proliferation and also stimulates them to IL-2 production. These results open a new potential applicability of ruthenium(III) complexes as a possible immune regulatory compound acting as immune suppressor at high concentration and as immune stimulator at low concentration.
authors: Laboratório de Genética Molecular e Citogenética, Instituto de Ciências Biológicas (ICB I), Universidade Federal de Goiás, Sala 200, Campus Samambaia (Campus II), Cx. Postal: 131, Goiânia, Goiás, Brazil. silveiralacerda@gmail.com
authors: Elisângela de Paula
authors: Ede P
authors: Silveira-Lacerda
authors: Cesar Augusto Sam Tiago
authors: CA
authors: Vilanova-Costa
authors: Flávia de Castro
authors: Fde C
authors: Pereira
authors: Amélia
authors: A
authors: Hamaguchi
authors: Luiz Alfredo
authors: LA
authors: Pavanin
authors: Luiz Ricardo
authors: LR
authors: Goulart
authors: Maria Inês
authors: MI
authors: Homsi-Brandenburgo
authors: Andreimar Martins
authors: AM
authors: Soares
authors: Wagner Batista
authors: WB
authors: dos Santos
authors: Auro
authors: A
authors: Nomizo
mesh_terms: D000328:Adult; D017304:Annexin A5 / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology; D049109:Cell Proliferation; D053938:DNA Fragmentation; D015195:Drug Design; D006801:Humans; D007107:Immune System; D007376:Interleukin-2 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D017975:Ruthenium Compounds / Q000494:pharmacology*; D014131:Trace Elements / Q000737:chemistry
chemical_list: C543901:(dichloro)tetraammineruthenium(III); D017304:Annexin A5; D000970:Antineoplastic Agents; D007376:Interleukin-2; D017975:Ruthenium Compounds; D014131:Trace Elements