Glutaric acidemia type I (GA-I) is an inherited
metabolic disease characterized by accumulation of
glutaric acid (GA) and
seizures. The intrastriatal GA administration in rats has been used as an animal model to mimic
seizures presented by glutaric acidemic patients.
m-Trifluoromethyl diphenyl diselenide, (m-CF(3) -C(6) H(4) Se)(2) , is an organoselenium compound that protects against
seizures induced by
pentylenetetrazole in mice. Thus, the aim of this study was to investigate whether (m-CF(3) -C(6) H(4) Se)(2) is effective against GA-induced
seizures and oxidative stress in rat pups 21 days of age. Our findings demonstrate that (m-CF(3) -C(6) H(4) Se)(2) preadministration (50 mg/kg; p.o.) protected against the reduction in latency and the increased duration of GA (1.3 μmol/right striatum)-induced
seizures in rat pups. In addition, (m-CF(3) -C(6) H(4) Se)(2) protected against the increase in reactive species generation and the reduction in
antioxidant defenses
glutathione peroxidase and
glutathione S-transferase activities induced by GA. By contrast, no change in
glutathione reductase or
catalase activities was found. In addition, (m-CF(3) -C(6) H(4) Se)(2) was effective in protecting against inhibition of Na(+) ,K(+) -
ATPase activity caused by GA in striatum of rat pups. This study showed for the first time that GA administration caused an increase in [(3) H]
GABA uptake from striatum slices of rat pups and that (m-CF(3) -C(6) H(4) Se)(2) preadministration protected against this increase. A positive correlation between duration of
seizures and [(3) H]
GABA uptake levels was demonstrated. The results indicate that (m-CF(3) -C(6) H(4) Se)(2) protected against GA-induced
seizures. Moreover, these findings suggest that the protection against oxidative stress, the inhibition of Na(+) ,K(+) -
ATPase activity, and the increase in [(3) H]
GABA uptake are possible mechanisms for the potential
anticonvulsant action of (m-CF(3) -C(6) H(4) Se)(2).