The SAS proposals for participation in FP6 projects
are listed in blocks according to the FP6 priority theme structure

FP6 priority
1.1.1   Genomics and Biotechnology for Health
Title of the proposal

Ischemia/reperfusion (e.g. stroke) induced injuries and their prevention by antioxidants derived from pyridoindol.

Slovak Academy of Sciences, Institute of Experimental Pharmacology
Dubravska cesta 9, 84216 Bratislava, Slovak Republic
Prof. Viktor BAUER, MD, DSc
+421 2 59410653

Research subject for a potential FP6 project

Ischemia/reperfusion with resulting tissue hypoxia/reoxygenation are frequently cause of remarkable local tissue injury in numerous pathologies (e.g. stroke, myocardial and intestinal infarction, inflammation, late diabetic complications) as well as in various conditions, such as transplantation, surgery, trauma. Number of data demonstrates that suppression of reactive free radicals generated under such conditions and/or elimination of their local deleterious effect may be exploited in prevention and/or such processes. Our interest is aimed at finding out new pharmacological substances with antiradical and protective properties even surpassing those of currently known antioxidants being devoid of side effects at the same time. In the Institute of Experimental Pharmacology of the Slovak Academy of Sciences a series of new water soluble pyridoindole antioxidants has been synthesized. Antioxidant property in some of them was found to be remarkable higher than in the prototype pyridoindole stobadine. Its antioxidant and scavenging properties, as well as its basic pharmaco-dynamic and toxicological profile were extensively studied and described. It was shown that stobadine protected various tissues and cells such as endothelium, nervous tissue, platelets against damaging action of disbalance between production and elimination of reactive oxygen species produced in vitro and in vivo. Infarct size in the heart after coronary occlusion and brain damage after carotid artery occlusion or trauma, as well as onset of late diabetic sequelae e.g. catarct, nephropathy, neuropathy was delayed by stobadine and some of its new congeners.

Recent international cooperation of the research team

R&D Project - Development and Basic Pharmacological Study of New Antioxidants; CENTAUR
Pharmaceuticals Inc., Sunnyvale CA, USA.
Cooperation with the Faculty of Medicine Fukuoka, Japan
Cooperation with the Institute of Physiology, Ukrainian Academy of Sciences, Kiev, Ukrainia

Proposerīs relevant publications related to the research subject

Bauer V., Matyas S., Stolc S., Sotnikova R., Nosalova V. (2001) Pathophysiology and Pharmacology of Reactive Oxygen Species (ROS). Reactive Oxygen Species as Mediators of Tissue Injury, Diseases and their Pharmacology.

Bauer V., Bauer F. (1999) Reactive oxygen species as mediators of tissue protection and injury. General Physiology and Biophysics 18, 7-14.
Bauer V., Sotnikova R., Machova J., Matyas S., Pucovsky V., Stefek M. (1999) Reactive oxygen species induced smooth muscle responses in the intestine, vessels and airways and the effect of antioxidants. Life Sciences 65, 1909-1917.
Horakova L., Stolc S. (1998) Antioxidant and pharmacodynamic effects of pyridoindole stobadine. A review. General Pharmacology 30, 627-638.
Nosalova V., Bauer V. (1999) Protective effect of stobadine in experimental colitis. Life Sciences 65, 1919-1921.
Soltes L., Bauer V., Bezek S., Ujhazy E. (2000) Extraction and chromatographic separation methods in pharmacological studies of stobadine – an indole-related antioxidant and free radical scavenger. Biomedical Chromatography 14/3, 188-201.
Stolc S. (1999) Indole deriatives as neuroprotectants. Life Sciences 65, 1943-1950.