In vitro and in vivo evaluation of kojic acid against Toxoplasma gondii in experimental models of acute toxoplasmosis

Background and Objective: Toxoplasma gondii (T. gondii) is a ubiquitous intracellular protozoan parasite that causes toxoplasmosis in humans and other warm-blooded animals. As current toxoplasmosis chemotherapies have many side effects along with toxicity on patients, we examined the anti-Toxoplasma effect of a biologically important natural antibiotic, kojic acid, in vitro and in vivo. Materials and Methods: Vero cells were incubated with different concentrations (1.56, 3.125, 6.25, 12.5, 25, 50, or 100 μg/mL) of kojic acid or pyrimethamine (positive control), and the cellular viability was determined. Next, Vero cells were infected with T. gondii (RH strain) and treated with drugs. Then, we calculated the infection index, T. gondii intracellular proliferation and the number and measure of plaque. Moreover, the effect of kojic acid (100 mg/kg/day) on survival times, serum levels of IFN-γ and TNF-α and histopathological changes in the liver and spleen of Balb/c mice infected with T. gondii were determined. Findings: Kojic acid reduced the infection index, intracellular proliferation, the number and measure of plaque in vitro when compared to untreated infected cells. Kojic acid (100 mg/kg/day) also showed a better survival rate than infected untreated control mice (P<0.05). IFN-γ and TNF-α secretions were significantly increased by kojic acid treatment in comparison to untreated groups (P<0.05). In addition, in liver tissues from kojic acid group, less and smaller areas with foci of inflammatory infiltrates were seen compared to infected and untreated mice. In spleen tissues, necrosis and foci of inflammatory infiltrates of the kojic acid group were negative similar to the pyrimethamine group. Conclusion: We conclude that kojic acid exhibit potent anti-Toxoplasma activity with direct and indirect effects on the parasite, although further studies are needed before consideration of clinical trials.

Keywords:

Toxoplasma gondii , Kojic Acid , In vitro , In vivo , Acute Toxoplasmosis