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Repurposing auranofin for treatment of Experimental Cerebral Toxoplasmosis
Iman Fathy Abou-El-Naga1, Nermine Mogahed Fawzy Hussein Mogahed2
1Professor of Parasitology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Purposes:
Evaluate the effect of auranofin on the early and late stages of chronic infection with Toxoplasma gondii avirulent ME49 strain.
Methods:
Swiss albino mice were orally inoculated with 10 cysts of Toxoplasma gondii, and orally treated with auranofin or septazole in daily doses of 20 mg/kg or 100 mg /kg, respectively, for 30 days. Treatment began either on the same day of infection and mice were sacrificed at the 60th day postinfection or the treatment started after 60 days of infection and mice were sacrificed at the 90th day postinfection.
Results:
Auranofin significantly reduced the brain cyst burden and inflammatory reaction at both stages of infection compared to the infected non-treated control. More remarkably, auranofin significant reduced the brain cyst burden in the late stage, while septazole failed. Hydrogen peroxide level was significantly increased in the brain homogenate of mice treated with auranofin only at the early stage of infection. Ultrastructral studies revealed that the anti-Toxoplasma effect of auranofin is achieved by changing the membrane permeability and inducing apoptosis.
Conclusions:
Thus, auranofin could be an alternative for the standard treatment regimen of toxoplasmosis and these results are considered another achievement for the drug against parasitic infection. Being a FDA-approved drug, it can be rapidly evaluated in clinical trials.
Insights
Auranofin effectively reduces brain cyst burden and inflammation in Toxoplasma gondii infections. This FDA-approved drug shows promise as an alternative treatment for toxoplasmosis, warranting clinical trials.
Area of Science:
- Parasitology
- Pharmacology
- Infectious Diseases
Background:
- Toxoplasmosis, caused by *Toxoplasma gondii*, is a significant public health concern.
- Current treatment options for toxoplasmosis have limitations and potential side effects.
- Exploring novel therapeutic agents is crucial for managing chronic *Toxoplasma gondii* infections.
Purpose of the Study:
- To evaluate the efficacy of auranofin against early and late stages of chronic *Toxoplasma gondii* infection.
- To compare the effects of auranofin with septazole, a standard treatment.
- To elucidate the mechanism of action of auranofin against *Toxoplasma gondii*.
Main Methods:
- Swiss albino mice were infected with *Toxoplasma gondii* ME49 strain.
- Mice received oral treatment with auranofin (20 mg/kg) or septazole (100 mg/kg) daily for 30 days.
- Treatment was initiated either concurrently with infection (early stage) or 60 days post-infection (late stage), with sacrifice at 60 or 90 days post-infection, respectively.
Main Results:
- Auranofin significantly reduced brain cyst burden and inflammation in both early and late infection stages compared to controls.
- Auranofin demonstrated superior efficacy in reducing late-stage brain cyst burden compared to septazole.
- Ultrastructural analysis indicated auranofin's anti-parasitic effect involves altering membrane permeability and inducing apoptosis.
Conclusions:
- Auranofin presents a viable alternative to current treatments for toxoplasmosis.
- The drug's efficacy against parasitic infections is further supported by these findings.
- As an FDA-approved medication, auranofin is suitable for expedited clinical evaluation.
