Could metformin modulate the outcome of chronic murine toxoplasmosis?

Toxoplasmosis is a pervasive parasitic infection possessing a chief impact on both public health and veterinary medicine. Unfortunately, the commercially-available anti-Toxoplasma agents have either serious side effects or diminished efficiency, specifically on the Toxoplasma tissue cysts. In the present study, metformin (The first-line treatment for type 2 diabetes mellitus) was investigated for the first time against chronic cerebral toxoplasmosis in mice model experimentally-infected with ME49 strain versus spiramycin. Two metformin regimens were applied; starting one week before the infection and four weeks PI. Parasitological, ultrastructural, histopathological, immunohistochemical, immunological, and biochemical assessments were performed. The anti-parasitic effect of metformin was granted by the statistically-significant reduction in tissue-cyst burden in both treatment regimens. This was accompanied by markedly-mutilated ultrastructure and profound amelioration of the cerebral histopathology with remarkable decline in the brain CD4⁺ and CD8⁺ T cell count. Besides, diminution of anti-Toxoplasma IgG and brain GSH levels was evident. Ultimately, the present findings highlighted the powerful promising therapeutic role of metformin in the management of chronic toxoplasmosis on a basis of anti-parasitic, anti-inflammatory, and anti-oxidant possessions.