Analysis of neuroprotective effects of propofol related compounds

L. DELGADO MARÍN; M. SÁNCHEZ-BORZONE; D. A. GARCIA

Córdoba

Congreso; 3º Reunión Internacional de Ciencias Farmacéuticas. 1º Jornada Internacional de Servicios Profesionales Farmacéuticos; 2014

CONICET, UNC, Universidad Nacional de Rosario, Facultad de Ciencias Químicas, Facultad de Ciencias Bioquímicas y Farmaceúticas

GABAA receptor (GABA-R), a ligand-gated ion channel, constitutes the main inhibitory receptor of the Central Nervous System. The GABA-R possesses binding sites for drugs other than the neurotransmitter GABA which behave as allosteric modulators. The known anaesthetic agent propofol, as well as other phenols studied by our group, have been shown to act on this receptor as positive allosteric modulators. These phenolic compounds also demonstrated an important antioxidant activity. Numerous investigative efforts have been promoted to identify pharmacologic agents that might reduce ischemic cerebral injury. Several compounds with GABAergic activity have shown neuroprotective effects attributed to their positive effects on GABA-R-mediated inhibition of synaptic transmission. Furthermore, it is important to remark that it was also found that antioxidant anesthetics, such as propofol, directly scavenge reactive oxygen species and inhibit lipid peroxidation leading to a neuroprotective result. In the present work, we investigated the neuroprotective effect of five phenolic compounds with gabaergic activity and with antioxidant properties (including propofol as reference compound), using primary cultures of cortical neurons which express functional GABA-R. Cell cultures were prepared from the cerebral cortices of 17-18 day-old rat fetuses and maintained in a DMEM supplemented with insulin, penicillin, and 10 % fetal calf serum. Following 6-7 days in vitro, the cells were exposed to different concentrations of each compound for 30 min or 24 h and cell viability was determined by lactate deshydrogenase release (LDH test). None compound demonstrated per se cytotoxic activity until 24 h of exposure. In addition, many of them exhibited partial protective effects against an injury model mediated by hydrogen peroxide. These results contribute to the understanding of the real neuroprotective mechanism exerted by anesthetics, involving pharmacological activity, an antioxidant effect or both actions mutually applied.