STUDIES ON THE EFFECT OF TWO ORGANOSELENIDE COMPOUNDS ON THE ACTIVITIES OF CEREBRAL DELTA AMINO LEVULINIC ACID DEHYDRATASE (ALA-D) AND Na+/K+ ATPase
*IJ Kade1,2; MW Paixão1; AL Braga1; G Zeni1; CW Nogueira1 and JBT Rocha1
1Postgraduate Programme in Biochemical Toxicology, Department of Chemistry, CCNE, Federal University of Santa Maria, CEP 97105-900, Camobi, Santa Maria, RS, Brazil.
2Department of Biochemistry, Federal University of Technology, PMB 704 Akure, Ondo State, Nigeria * Corresponding author, e-mail: ijkade@yahoo.com
Organoselenide compounds have been documented as promising pharmacological agents against a number of diseases induced by oxidative stress. This has elicited an increased interest in the synthesis and biological testing of novel organodiselenides. An organodiselenide derived from cholesterol molecule (cholesteryl diselenide) was recently synthesized in our laboratory. Following a report indicating that organoselenide compounds generally posses a central effect on mammalian systems, the present study therefore sought to evaluate the effect of this novel compound and diphenyl diselenide on ALA-D and Na+/K+-ATPase activities in the rat brain. We also evaluated the glutathione (GSH) peroxidase mimetic activity of the two compounds as well as their ability to oxidize mono- and di- thiols. The antioxidant effect were tested by measuring the ability of the compounds to inhibit the formation of thiobarbituric acid reactive species (TBARS) induced by neurotoxic agents such as iron and sodium nitroprusside, and also their ability to inhibit the formation of protein carbonyls induced by iron.
The results show that diphenyl diselenide exhibited a higher GSH- peroxidase mimetic activity as well as increased ability to oxidize both mono- and di- thiols than the cholesteryl diselenide. In addition, while diphenyl diselenide inhibited the formation of TBARS and protein carbonyls in a concentration dependent manner, the cholesteryl diselenide exhibited a prooxidant effect in all the concentration range (20-167mM) tested. Our results also show that while ALA-D was completely inhibited by diphenyl diselenide at 10mM, it was only weakly inhibited by the cholesteryl diselenide at 100mM. In addition, another thiol (SH) containing protein, Na+/K+ ATPase, was inhibited by diphenyl diselenide (greater than 70% at 200mM) while the cholesteryl diselenide had a weak (less than 20% at 200mM) inhibitory effect on the activity of the enzyme. Further studies reveal that the inhibition of Na+/K+ ATPase by diphenyl diselenide likely involves the modification of the ATP binding site of the enzyme. In conformity with our earlier observation, we conclude that the inhibition of Na+/K+ ATPase by organodiselenides, possibly involves the modification of the SH group at the active site of the enzyme.
Supported by CNPq/TWAS, FAPERGS, CAPES, VITAE
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