FP6 priority

1.1.1   Genomics and Biotechnology for Health

1.1.2

Title of the proposal

Antioxidants in the elimination of developmental toxicity induced by oxidative stress and its consequences on the nervous system

Institute

Slovak Academy of Sciences, Institute of Experimental Pharmacology
Dubravska cesta 9, 842 16 Bratislava and Cancer Research Institute, Vlarska 7, 833 91 Bratislava, Slovak Republic

Contact

Research subject for a potential FP6 project

Oxidative stress is a serious risk factor of tissue and organ damage in the developing foetus, insufficiently equipped by antioxidative enzymatic systems. Brain damage as the consequence of brain ischaemia in development remains a major cause of perinatal mortality and chronic neurological morbidity. During delivery marked circulatory and respiratory changes occur, which consequently lead to oxidative stress. This fact is very important especially in the case of premature delivery in human beings as well as in experimental animals. Antioxidants play an important role in the prophylaxis and therapy of neurological diseases induced by oxidative stress. Objectives of the project: evaluation of preventive effect of antioxidants on prenatal hypoxia induced changes in pre- and postnatal development in rats as well as study of the preventive effect on neonatal asphyxia induced changes in functional development of the CNS in rat offspring from birth to adulthood. To evaluate the neurobehavioural development the following methods will be used: transplacental micronucleus test and comet assay for evaluation of chromosomal and DNA lesions in foetuses; biochemical analysis of enzyme systems in organs of mothers and foetuses (GSH/GSSG status, lysosomal enzymes); HPLC method for determination of biochemical variables of neurotransmitter systems in selected brain regions; histological examination of the brain; methods of ethological analysis of behaviour (neuromotor and reflex development, sensory function, levels of activity and emotional reactivity, learning and memory processes).

Recent international cooperation of the research team

Laboratory of Histology and Embryology, Medical Faculty of Aristotle University, Tessaloniki, Greece; Department of Pharmacology and Toxicology, Charles University, Faculty of Medicine, Plzen, Czech Republik

Proposer´s relevant publications related to the research subject

Dubovicky M., Ujhazy E., Kovacovsky P., Rychlik I., Jansak J.: Evaluation of long-term administration of the antioxidant stobadine on exploratory behavior in rats of both genders. J. Appl. Toxicol. 19, 1999, 431-436; Dubovicky M., Ujhazy E., Kovacovsky P., Mach M.: Effect of repeated administration of the antioxidant stobadine on the behaviour of singly-housed male mice in intraspecies conflict. Methods Find. Exp. Clin. Pharmacol. 23, 2001, 491-495; Navarova J., Macickova T., Horakova K., Urbancikova M.: Stobadine inhibits lysosomal enzyme release in vivo and in vitro. Life Sciences 65, 1999, 1905-1907; Slamenova D., Gabelova A., Ruzekova L., Chalupa I., Horvathova E. Farkasova T., Bozsakyova E., Stětina R.: Detection of MNNG-induced DNA lesions in mammalian cells; Validation of comet assay against DNA unwinding technique, alkaline elution of DNA and chromosomal aberrations. Mutat. Res. 383, 1997, 243-252.