Modulation of creatine kinase activity by ruthenium complexes.
Creatine kinase is a crucial enzyme for brain, heart and skeletal muscle energy homeostasis, and a decrease of its activity has been associated with cell death. Many biological properties have been attributed to ruthenium complexes. In this context, this work was performed in order to evaluate creatine kinase activity from rat brain, heart and skeletal muscle (quadriceps) after administration of ruthenium complexes, trans-[RuCl(2)(nic)(4)] (nic=3-pyridinecarboxylic acid) 180.7 micromol/kg (complex I), trans-[RuCl(2)(i-nic)(4)] (i-nic=4-pyridinecarboxylic acid) 13.6 micromol/kg (complex II), trans-[RuCl(2)(dinic)(4)] (dinic=3,5-pyridinedicarboxylic acid) 180.7 micromol/kg (complex III) and trans-[RuCl(2)(i-dinic)(4)] (i-dinic=3,4-pyridinedicarboxylic acid) 180.7 micromol/kg (complex IV). Our results showed that complex I caused inhibition of creatine kinase activity in hippocampus, striatum, cerebral cortex, heart and skeletal muscle. Besides, complex II did not affect the enzyme activity. complexes III and IV increased creatine kinase activity in hippocampus, striatum, cerebral cortex and heart, but not in skeletal muscle. Besides, none of the complexes in vitro altered creatine kinase activity, suggesting that enzymatic activity is indirectly affected by complexes I, III and IV. It is believed that diminution of creatine kinase in brain of rats caused by complex I may be related to results from other study reporting memory impairment caused by the same complex. Further research is necessary in order to elucidate the effects of ruthenium complexes in other important metabolic enzymes.
Zanette
Francine
F
Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil.
Victor
Eduardo G
EG
Scaini
Giselli
G
Di-Pietro
Priscila B
PB
Cardoso
Danon C
DC
Cristiano
Maykon P
MP
Dal-Pizzol
Felipe
F
Paula
Marcos M S
MM
Streck
Emilio L
EL
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D003402:Creatine Kinase / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D007539:Isonicotinic Acids / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D015394:Molecular Structure; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D009539:Nicotinic Acids / Q000737:chemistry / Q000494:pharmacology; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology*
D007539:Isonicotinic Acids; D009539:Nicotinic Acids; D009942:Organometallic Compounds; C403903:dichlorotetrakis(3,5-pyridinedicarboxylic acid)ruthenium(II); C440900:dichlorotetrakis(isonicotinic acid)ruthenium(II); C440899:dichlorotetrakis(nicotinic acid)ruthenium(II); D012428:Ruthenium; D003402:Creatine Kinase