ABSTRACT: Toxoplasma gondii is a common intracellular protozoal infection of humans worldwide. Severe disease can occur in immunocompromised individuals and non-immune pregnant women can infect their offspring. Chronic infection is associated with vision and hearing problems and functional mental alterations including schizophrenia. The mood stabilizing agent valproic acid has been shown to inhibit the development of T. gondii in vitro at dosages that are normally achieved in the serum and cerebral spinal fluid of human patients and to have positive effects on the behavior of rats chronically infected with T. gondii. The present study was done to examine the in vivo activity of valproic acid against acute toxoplasmosis in mice. Two studies were done giving valproic acid in the drinking water at a concentration of 1.5 mg/ml (Experiment 1) or 3.0 mg/ml (Experiment 2). In a third experiment (Experiment 3), valproic acid was injected intraperitoneally (i.p.) at doses of 200 or 300 mg/kg every 12 hr. Valproic acid was not effective in preventing acute toxoplasmosis. All mice treated with valproic acid died or were killed and did not significantly (P >0.05) live longer than the controls. Tachyzoites were demonstrated in the tissues of infected valproic acid treated mice. Our results indicate that valproic acid, while effective in vitro against T. gondii tachyzoites, is not effective as a preventative in mice inoculated with T. gondii tachyzoites.
Journal of Parasitology 03/2008; · 1.40 Impact Factor