Rosuvastatin reduced brain parasite burden in a chronic toxoplasmosis in vivo model and influenced the neuropathological pattern of ME-49 strain

Abstract

This study evaluated the effects of rosuvastatin in vivo on toxoplasmosis chronic infection. Thirty-five Swiss mice were orally infected (ME-49 strain). After 50 days, the mice were separated into five groups: GI – non-infected, GII – infected, GIII – infected and treated with pyrimethamine and sulfadiazine (12.5 + 50 mg kg−1 body weight day−1), GIV and GV – infected and treated with rosuvastatin 10 and 40 mg kg−1 body weight day−1, respectively. After 21 days, we collected blood, liver, lungs, femoral biceps and brain were removed for Toxoplasma gondii DNA quantification by qPCR and histopathological analysis. GIV and GV did not present premature death or clinical changes, and the hepatic enzyme levels were lower compared to GI. Toxoplasma gondii DNA was detected mainly in brain and muscle, but the parasite load was significantly lower in GV compared to GII brains (P < 0.05). Histopathological changes were observed in brains, with T. gondii cysts as well as an inflammatory condition, including necrosis areas in GII and GIII. These data confirm active infection with tissue injury. This inflammatory condition was attenuated in the groups treated with rosuvastatin, especially R40 (GV). Our findings demonstrated the in vivo action of rosuvastatin in reducing cerebral parasitic load and indicate that this drug may interfere in chronic toxoplasmosis.

Effect of Statin Use on the Clinical Manifestations, Laboratory Test Results and Outcome of Lyme Neuroborreliosis

“…Statins are cholesterol-lowering drugs and are widely used for the prevention of cardiovascular disease. Because of their anti-inflammatory, as well as their antimicrobial activity [4][5][6] along with additional evidence that statins may reduce neuro-inflammation and blood-brain barrier dysfunction [7][8][9], numerous clinical studies have assessed their impact on the outcome of many different infectious diseases [10][11][12][13][14][15][16][17]. However, although statins were reported to have beneficial effects in a murine model of Lyme borreliosis [18], we were unable to find any report on the impact of statins on the severity or course of Lyme borreliosis in humans.…”

Ginger Is a Potential Therapeutic for Chronic Toxoplasmosis

“…A histopathological examination of the brains of infected untreated mice showed pathological lesions which included T. gondii cysts, edema, red neurons and chronic inflammatory cell infiltrate. We believe that these lesions are caused by a disruption of blood–brain barrier and invasion of brain tissue by the parasite [ 15 ]. T. gondii infection-induced pathological changes in the brain are potentially due to high oxidative stress, high levels of nitric oxide production, glial activation and apoptosis [ 4 , 15 , 44 , 45 , 46 ].…”

“…We believe that these lesions are caused by a disruption of blood–brain barrier and invasion of brain tissue by the parasite [ 15 ]. T. gondii infection-induced pathological changes in the brain are potentially due to high oxidative stress, high levels of nitric oxide production, glial activation and apoptosis [ 4 , 15 , 44 , 45 , 46 ]. In the present study, treatment of T. gondii -infected mice with ginger extract resulted in a marked improvement of T. gondii infection-induced brain pathological changes.…”

“…Currently, there are limited effective therapeutic options for toxoplasmosis with no optimal effective treatment for chronic toxoplasmosis due to poor penetration into the brain and potential side effects [ 15 , 16 , 17 , 18 , 19 ]. The combination of pyrimethamine and sulfadiazine (pyr-sulf), targeting the active stage of the infection and suppressing parasite multiplication in the early stages of the disease, is the current gold standard for treating toxoplasmosis [ 15 , 16 ].…”

“…Currently, there are limited effective therapeutic options for toxoplasmosis with no optimal effective treatment for chronic toxoplasmosis due to poor penetration into the brain and potential side effects [ 15 , 16 , 17 , 18 , 19 ]. The combination of pyrimethamine and sulfadiazine (pyr-sulf), targeting the active stage of the infection and suppressing parasite multiplication in the early stages of the disease, is the current gold standard for treating toxoplasmosis [ 15 , 16 ]. However, several side effects have been reported for this medication including neutropaenia, decreased platelet count, thrombocytopaenia, leucopaenia, elevated serum creatinine and liver enzymes, and hypersensitivity reactions [ 20 ].…”