The Effect of a Cysteine Protease Inhibitor on Schistosoma mansoni : In Vitro and In Vivo Experimental Studies

Abstract

S. mansoniis a blood fluke responsible for the chronic human diseaseschistosomiasis mansoni,the second endemic disease worldwide, with high-prevalence endemicity in Egypt.Infection occurs by contact with fresh water that contains the cercariae which penetrate intact skin and transform into schistosomula that travel through the blood stream before differentiating into male and female adult worms.The immunopathology of schistosomiasismansoni is due to delayedhypersensitivity reaction which results in granuloma formation around eggs leading toobstructive intestinal disease, hepatosplenic inflammation and liver fibrosis.

PZQ is the mainstay of schistosomiasis treatment. However, PZQ is not effective against the larval stages of schistosomes, it also does not prevent re-infection with the possibility of emergence of drug resistance.

CPs play numerous roles in the biology of parasites. Despite the presence of host homologues,the difference in nature between parasite CPsand the host proteins has given chances for its use as a target for chemotherapy. Theschistosome digestive tract digests the macromolecules derived from mammalian hostblood then absorb the soluble products by several proteases. Thereby, CPIs would compromise S. mansoni development inside the host and lead them to death through starvation.

The current work was done to study the effect of phenyl vinyl sulphone (PVS), a CPI, on different stages of S. mansoni in an in vitro study, and on the parasite subjected to PVS at different durations of schistosomiasis mansoni in experimentally-infected mice, in comparison to the conventionally employed drug; praziquantel (PZQ).

As regards in vitro study, the S.mansonischistosomula and adult worms were maintained, separately, in RPMI-1640 medium.Then were subjected to different concentrations of PVS(1 µg/ml, 2 µg/ml, 4 µg/ml, 6µg/ml, 8µg/ml and 10 µg/ml).Positive and negativecontrols (PZQ at 1 μg/ml and DMSO) were also studied.

S.mansoni schistosomula and adults were kept for a 4- and 6- dayperiod, respectively, and monitored every 24 hours. The parameters used for the in vitro study were: A) Dose-response studies by detection of the percent worm mortality for each of S. mansoni schistosmoula and adult worms. B) Growth inhibition studies by detection of hemoglobin degradation for schistosomula and oviposition for adults.