Chemico-Biological Interactions 170 (2007) 59–66
Effect of ruthenium complexes on the activities of succinate
dehydrogenase and cytochrome oxidase
Eduardo G. Victor
a,b
, Francine Zanette
b
, Maira R. Aguiar
b
,
Claudia S. Aguiar
b
, Danon C. Cardoso
a
, Maykon P. Cristiano
a
,
Emilio L. Streck
b,∗
, Marcos M.S. Paula
a
a
Laborat´ orio de S´ ıntese de Complexos Multifuncionais, Universidade do Extremo Sul Catarinense, 88806-000 Crici´ uma, SC, Brazil
b
Laborat´ orio de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, 88806-000 Crici´ uma, SC, Brazil
Received 26 April 2007; received in revised form 4 July 2007; accepted 5 July 2007
Available online 12 July 2007
Abstract
In this article, we report the effects of acute administration of ruthenium complexes, trans-[RuCl
2
(nic)
4
] (nic = 3-
pyridinecarboxylic acid) 180.7 mol/kg (complex I), trans-[RuCl
2
(i-nic)
4
] (i-nic = 4-pyridinecarboxylic acid) 13.6 mol/kg
(complex II), trans-[RuCl
2
(dinic)
4
] (dinic = 3,5-pyridinedicarboxylic acid) 180.7 mol/kg (complex III) and trans-[RuCl
2
(i-
dinic)
4
]Cl (i-dinic = 3,4-pyridinedicarboxylic acid) 180.7 mol/kg (complex IV) on succinate dehydrogenase (SDH) and cytochrome
oxidase (COX) activities in brain (hippocampus, striatum and cerebral cortex), heart, skeletal muscle, liver and kidney of rats. Our
results showed that complex I inhibited SDH activity in hippocampus, cerebral cortex, heart and liver; and inhibited COX in heart
and kidney. Complex II inhibited SDH in heart and hippocampus; COX was inhibited in hippocampus, heart, liver and kidney. SDH
activity was inhibited by complex III in heart, muscle, liver and kidney. However, COX activity was increased in hippocampus,
striatum, cerebral cortex and kidney. Complex IV inhibited SDH activity in muscle and liver; COX activity was inhibited in kidney
and increased in hippocampus, striatum and cerebral cortex. In a general manner, the complexes tested in this work decrease the
activities of SDH and COX in heart, skeletal muscle, liver and kidney. In brain, complexes I and II were shown to be inhibitors and
complexes III and IV activators of these enzymes. In vitro studies showed that the ruthenium complexes III and IV did not alter
COX activity in kidney, but activated the enzyme in hippocampus, striatum and cerebral cortex, suggesting that these complexes
present a direct action on COX in brain.
© 2007 Elsevier Ireland Ltd. All rights reserved.
Keywords: Ruthenium; Succinate dehydrogenase; Cytochrome oxidase; Mitochondria
1. Introduction
Previous research in our laboratory described the syn-
thesis and characterization of new trans-[RuCl
2
(L)
4
]
complexes, where L is pyridinecarboxylic acids deriva-
∗
Corresponding author. Fax: +55 48 3431 2644.
E-mail address: emiliostreck@terra.com.br (E.L. Streck).
tive ligand [1–3]. The employ of ligand containing car-
boxylic or dicarboxylic acid groups provides reasonable
solubility of complexes in physiological medium. These
complexes are suitable for biological and pharmacologi-
cal applications. The ruthenium coordination complexes
tested in this work were trans-[RuCl
2
(nic)
4
] (nic = 3-
pyridinecarboxylic acid) (complex I), trans-[RuCl
2
(i-
nic)
4
] (i-nic = 4-pyridinecarboxylic acid) (complex II),
trans-[RuCl
2
(dinic)
4
] (dinic = 3,5-pyridinedicarboxylic
0009-2797/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.cbi.2007.07.001