Acetazolamide as a novel therapeutic agent against acute experimental toxoplasmosis: Insights into carbonic anhydrase inhibition.

Abstract

Although the current therapeutic regimens for acute toxoplasmosis, most commonly a combination of pyrimethamine and sulfadiazine, are still considered the standard of care, they are associated with numerous drawbacks, such as bone marrow suppression, and hepatotoxicity. Given these challenges, there is an urgent need to explore and find safer and more effective therapeutic alternatives. Acetazolamide has been widely used in clinical practice for non-infectious illnesses. Lately, increasing attention has been directed toward its repurposing as an antiparasitic agent. Thirty-six mice were infected with Toxoplasma gondii (RH strain) tachyzoites, and divided into three groups: non-treated group, Acetazolamide-treated group and Septrin- treated group. In the present study, the anti - Toxoplasma efficacy of Acetazolamide was assessed in comparison to Septrin using parasitological, ultrastructural, biochemical, immunological, and histopathological studies. Treatment with Acetazolamide significantly prolonged the mice's survival time and reduced tachyzoites count with percentages of reduction of 83.12% and 79.84 % in the peritoneal fluids and hepatic impression smears, respectively. Furthermore, Acetazolamide has dramatically altered the ultrastructure of the tachyzoites, decreased the liver and kidney malondialdehyde levels and suppressed serum cytokines (tumor necrosis factor alpha and interleukin-1β). Histopathological examination of hepatic and renal tissue sections showed amelioration of parenchymal inflammation and scanty parasite. In conclusion, Acetazolamide demonstrated a significant promise as a therapeutic agent for combating acute murine toxoplasmosis with anti-inflammatory and antioxidant effects.