Effect of HIV aspartyl protease inhibitors on experimental infection with a cystogenic Me49 strain of Toxoplasma gondii.

Toxoplasmosis is a zoonotic disease of major significant perspectives in public health and veterinary medicine. So far, the available drugs control only the active infection, once the parasite encysts in the tissues, they lose their efficacy. Cytokines; IFN-γ and IL-10, play a critical role in the modulation of toxoplasmic encephalitis and neuro-inflammation in chronic toxoplasmosis. Antiretroviral protease inhibitors applied in the treatment of acquired immunodeficiency syndrome, revealed activity against multiple parasites. Aluvia (lopinavir/ritonavir) (L/R); an aspartyl protease inhibitor, had efficiently treated T. gondii RH strain infection. We investigated the potential activity of L/R against experimental T. gondii infection with a cystogenic Me49 strain in mice, considering the role of IFN-γ and IL-10 in the neuropathology versus pyrimethamine-sulfadiazine combination therapy. Three aluvia regimens were applied; starting on the day of infection (acute phase), 2-week PI (early chronic phase) and eight weeks PI (late chronic phase). L/R reduced the brain-tissue cyst burden significantly in all treatment regimens. It impaired the parasite infectivity markedly in the late chronic phase. Ultrastructural changes were detected in Toxoplasma cyst membrane and wall, bradyzoite membrane and nuclear envelope. The signs of bradyzoite paraptosis and cytoplasmic lipid droplets were observed. L/R had significantly reduced the brain-homogenate levels of IFN-γ and IL-10 in its three regimens however, they could not reach the normal level in chronic phases. Cerebral hypercellularity, perivascular inflammatory response, lymphoplasmacytic infiltrates and glial cellular reaction were ameliorated by L/R treatment. Herein, L/R was proved to possess promising preventive and therapeutic perspectives in chronic cerebral toxoplasmosis.

Cardioprotective effect of cerium oxide nanoparticles in monocrotaline rat model of pulmonary hypertension: A possible implication of endothelin-1.

AIMS: Cerium oxide nanoparticles (CeO2NPs) have been recently introduced into the medical field for their antioxidant properties. The ability of CeO2NPs alone or in combination with spironolactone (SP) to attenuate monocrotaline (MCT)-induced pulmonary hypertension and associated right ventricular hypertrophy was studied in rats. A special emphasis was given to endothelin-1 pathway. MATERIALS AND METHODS: Pulmonary hypertension was induced in albino rats by a single subcutaneous injection of MCT (60 mg/kg). Rats received either single CeO2NPs therapy or combined therapy with SP for 2 weeks. KEY FINDINGS: CeO2NPs improved pulmonary function tests with concomitant decrease in serum endothelin-1 and pulmonary expression of endothelin-1 and its receptor ETAR. Besides, CeO2NPs diminished MCT-induced right ventricular hypertrophy and reduced cardiac oxidative stress and apoptosis. SIGNIFICANCE: CeO2NPs could improve pulmonary hypertension and associated right ventricular hypertrophy with no additive value for SP. Besides being an antioxidant, CeO2NPs work through endothelin-1 pathway to improve pulmonary hypertension.