الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Schistosomiasis is a major parasitic disease that affects 170 million people in sub-Saharan Africa and almost 30 million people in north of Africa, Asia and South America. Shistosoma mansoni, the causative agent of intestinal schistosomiasis, is acquired by human contact with fresh water containing infectious cercariae. Egg deposition in the liver is associated with the formation of granulomas and subsequent serious complications. Up till now praziquantel (PZQ) is the drug of choice in schistosomiasis, as recommended by the WHO. However, the threat of development of PZQ resistance is expected at any time, and grows real concerns about reliance on PZQ only. So, there is always an urgent need to search for new therapeutic targets in Schistosoma, and to investigate other therapeutic lines for such dramatically morbid parasitic infection. As occurs during the life cycle of Plasmodium species in the human body, schistosomal worms need to consume large amounts of hemoglobin to complete their development and sexual maturation. Hemoglobin hydrolysis results in the release of a lipophilic iron-containing compound of porphyrin termed heme, which represents the non-protein part of hemoglobin. Such released heme molecule is highly toxic to the worm as it interacts with its membranes, to end up with killing the worm by oxidative stress reactions. To avoid the toxic effect of heme, the worm gut is provided with polymerase enzymes to detoxify the heme molecule into a non-toxic crystallized molecule termed “hemozoin”. The released Hz becomes subsequently engulfed by blood monocytes and tissue macrophages in the different lymphoid organs. In addition to the portal hypertension in schistosomiasis, high levels of Hz were found to correlate positively with the severity of schistosomal splenomegaly as occurs in malaria. Interestingly, both Plasmodium & Schistosoma species use the same mechanism for heme detoxication. Hence, using antimalarials that act on the inhibition of heme detoxification process is now precisely investigated for the treatment of schistosomiasis. A recent study has reported a decrease in macrophage (M1) activation, proliferation and phagocytic activity after the administration of a prolonged course of PZQ in S. japonicum-infected mice. Surprisingly, these findings were also associated with splenomegaly amelioration and a decrease in M1 NLRP3 inflammasome expression. Chloroquine is a quinoline compound that is considered the most widely used anti-malarial drug, except in chloroquine resistant P. falciparum cases. The main mechanism of action of CLQ is to inhibit the parasitic heme polymerase enzyme. Chloroquine has attracted much attention recently for its anti-inflammatory and anti-phagocytic properties by NLRP3 inflammasome manipulation. This study aims to: investigate the therapeutic effect of CLQ on experimental Schistosoma mansoni infection compared to PZQ and explore the possible effect of both drugs on schistosomal splenomegaly. This study was conducted on 180 male Swiss albino mice (140 S. mansoni-infected & 40 non infected mice).