Trichinella spiralis: A new parasitic target for curcumin nanoformulas in mice models.

Trichinosis spiralis is a global disease with significant economic impact. Albendazole is the current-treatment. Yet, the world-widely emerging antimicrobial resistance necessitates search for therapeutic substitutes. Curcumin is a natural compound with abundant therapeutic benefits. This study aimed to evaluate the potential of crude-curcumin, chitosan and for the first time curcumin-nano-emulsion and curcumin-loaded-chitosan-nanoparticles against Trichinella spiralis adults and larvae in acute and chronic trichinosis models. Trichinosis spiralis was induced in 96 Swiss-albino mice. Infected mice were divided into 2 groups. Group I constituted the acute model, where treatment started 2 h after infection for 5 successive days. Group II constituted the chronic model, where treatment started at the 30th day-post-infection and continued for 10 successive days (Refer to graphical abstract). Each group contained 8 subgroups that were designated Ia-Ih and IIa-IIh and included; a; Untreated-control, b; Albendazole-treated (Alb-treated), c; Crude-curcumin-treated (Cur-treated), d; Curcumin-nanoemulsion-treated (Cur-NE-treated), e; Albendazole and crude-curcumin-treated (Alb-Cur-treated), f; Albendazole and curcumin-nanoemulsion-treated (Alb-Cur-NE-treated), g; Chitosan-nanoparticles-treated (CS-NPs-treated) and h; Curcumin-loaded-chitosan-nanoparticles-treated (Cur-CS-NPs-treated). Additionally, six mice constituted control-uninfected group III. The effects of the used compounds on the parasite tegument, in-vivo parasitic load-worm burden, local pathology and MDA concentration in small intestines of acutely-infected and skeletal muscle of chronically-infected mice were studied. Results showed that albendazole was effective, yet, its combination with Cur-NE showed significant potentiation against adult worms and muscle larvae and alleviated the pathology in both models. Cur-CS-NPs exhibited promising results in both models. Crude-curcumin showed encouraging results especially against muscle larvae on long-term use. Treatments effectively reduced parasite load, local MDA level and CD31 expression with anti-inflammatory effect in intestine and muscle sections.

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.