title: Oxidative stress induced by the Fe/ascorbic acid system or model ischemia in vitro: effect of carvedilol and pyridoindole antioxidant SMe1EC2 in young and adult rat brain tissue.
abstract: New effective strategies and new highly effective neuroprotective agents are being searched for the therapy of human stroke and cerebral ischemia. The compound SMe1EC2 is a new derivative of stobadine, with enhanced antioxidant properties compared to the maternal drug. Carvedilol, a non-selective beta-blocker, possesses besides its cardioprotective and vasculoprotective properties also an antioxidant effect. We compared the effect of carvedilol and SMe1EC2, antioxidants with a similar chemical structure, in two experimental models of oxidative stress in young and adult rat brain tissue. SMe1EC2 was found to improve the resistance of hippocampal neurons to ischemia in vitro in young and even in 18-month-old rats and inhibited formation of protein carbonyl groups induced by the Fe(2+)/ascorbic acid pro-oxidative system in brain cortex homogenates of young rats. Carvedilol exerted a protective effect only in the hippocampus of 2-month-old rats and that at the concentration 10-times higher than did SMe1EC2. The inhibitory effect of carvedilol on protein carbonyl formation induced by the pro-oxidative system was not proved in the cortex of either young or adult rats. An increased baseline level of the content of protein carbonyl groups in the adult versus young rat brain cortex confirmed age-related changes in neuronal tissue and may be due to increased production of reactive oxygen species and low antioxidant defense mechanisms in the adult rat brain. The results revealed the new pyridoindole SMe1EC2 to be more effective than carvedilol in neuroprotection of rat brain tissue in both experimental models involving oxidative stress.
authors.affiliation: Institute of Experimental Pharmacology & Toxicology, Slovak Academy of Sciences, SK-84104 Bratislava, Slovakia.
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Gáspárová
authors.forename: Olga
authors.initials: O
authors.lastname: Ondrejičková
authors.forename: Alena
authors.initials: A
authors.lastname: Gajdošíková
authors.forename: Andrej
authors.initials: A
authors.lastname: Gajdošík
authors.forename: Vladimír
authors.initials: V
authors.lastname: Snirc
authors.forename: Svorad
authors.initials: S
authors.lastname: Stolc