AMELORATIVE AND HEPATOPROTECTIVE EFFECTS OF FISETIN ON ACUTE MURINE TOXOPLASMOSIS

Toxoplasma gondii (T. gondii) protozoan invades any nucleated cell with a special predilection toreticuloendothelial cells. Liver is severely affected during acute toxoplasmosis. Promisingly, fisetin(FIS) flavonoid was proved to have antioxidant, anti-inflammatory, anti-cancerous, and anti-protozoaleffects. This study was designed to evaluate the anti-Toxoplasma effect and the hepatoprotective potentialof FIS in vivo. Mice were infected with the virulent RH strain of T. gondii in a dose of1x103tachyzoites/mouse. Mice were divided into seven equal groups: G1: healthy control, G2: infectedcontrol, G3: Pyrimethamine® (PYR)/sulfadiazine (SDZ)), G4: oral-FIS, G5: oral-FIS+ PYR treated,G6: intraperitoneal (I.P) FIS, and G7: I.P FIS+PYR treated. Survival rate was estimated, and tachyzoiteswere counted in liver impression smears. Liver enzymes and C reactive protein (CRP) were measuredin mice sera. Liver tissues were examined for inflammatory mediators; cyclooxygenase 2 (COX-2), interleukin (IL) -10, IL-12, IL- , oxidative mediators; inducible nitric oxide synthase (iNOS),myeloperoxidase (MPO), and malondialdehyde (MDA) FIS showed a moderate effect on parasite survivaland tachyzoites count, with an excellent effect in reducing serum liver enzymes activity and proinflammatorymediators. Combined (FIS+PYR) showed the best anti-parasitic and hepatoprotectiveactions. Its administration I.P. gave significant cure compared to oral route. FIS when given I.P thanoral FIS had a good anti-inflammatory and antioxidant effect, decreased inflammatory cytokines andimproved hepatic pathology of acute toxoplasmosis. Combined FIS/PYR was the best drug regimen.