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. 2017 Dec;41(4):1049-1058.
doi: 10.1007/s12639-017-0933-3. Epub 2017 Jun 22.

Effect of phenyl vinyl sulphone cysteine protease inhibitor on Schistosoma mansoni: in vitro and in vivo experimental studies

Manal Salah El-Din Mahmoud  1 , Ayman Nabil Ibrahim  1 , Abeer Fathy Badawy  1 , Nourhan Mohamed Abdelmoniem  1
Affiliations

Effect of phenyl vinyl sulphone cysteine protease inhibitor on Schistosoma mansoni: in vitro and in vivo experimental studies

Manal Salah El-Din Mahmoud et al. J Parasit Dis. 2017 Dec.

Abstract

The present work aimed to study the effect of phenyl vinyl sulphone (PVS), a CPI, on different stages of Schistosoma (S.) mansoni in an in vitro culture study and in experimentally infected mice, compared to PZQ. As regards the in vitro study, different concentrations of PVS (1, 2, 4, 6, 8 and 10 µg/ml) and PZQ (1 µg/ml) were assessed by % worm mortality for schistosomula and adults, and hemoglobin degradation by schistosomula. In vivo study included 8 groups of mice. Intraperitoneal PVS, subgroup (a), and oral PZQ, subgroup (b), were assessed at different durations post infection (pi); at 1, 3, 5 and 7 weeks pi (groups I, II, III and IV, respectively). Infection, PVS, PZQ, and normal control groups (groups V-VIII) were included. The anti-schistosomal effects of PVS were assessed by parasitological, histopathological and haematological parameters. In in vitro study, PVS had a schistosomicidal effect in a concentration and time dependent manner, PVS showed 100% schistosomula mortality at day 2 and 92% adult worm mortality at day 5. Furthermore, PVS decreased hemoglobin degradation by schistosomula. In in vivo study, PVS showed a decrease in total worm burden and tissue egg load in intestine and liver with an increase in number of dead ova in intestine of mice. Furthermore, PVS resulted in a decrease in number, size and cellularity of hepatic granulomas and an increase in hemoglobin concentration.PVS was better than PZQ in reducing each of tissue egg count in intestine at 5 and 7 weeks pi, and hepatic granuloma size at 3, 5 and 7 weeks pi. These results suggest that PVS can be a promising chemotherapeutic agent in Schistosoma mansoni infection.

Keywords: Cysteine protease; Cysteine protease inhibitor; In vitro; In vivo; Phenyl vinyl sulphone; Praziquantel; Schistosoma mansoni.

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Conflict of interest statement

Conflict of interest

We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us.

Ethical approval

The study was approved by the Research Ethics Committee, Faculty of Medicine, Ain Shams University. All the animal experiments were performed according to the rules and regulation of the Animal Ethics rules, Ain-Shams University, Cairo, Egypt.

Figures

Fig. 1
Fig. 1
Bar chart illustrating the effect of different concentrations of PVS on the mortality of schistosomula in comparison to PZQ and DMSO controls. The IC50 of PVS was 7.5 µg/ml at day 1, 4 µg/ml at day 2 and 2.5 µg/ml at day 3
Fig. 2
Fig. 2
Bar chart illustrating the effect of different concentrations of PVS on the viability of S. mansoni adult worms in comparison to PZQ and DMSO controls. The IC50 of PVS was 6 µg/ml at day 4 and 3.9 µg/ml at day 5
Fig. 3
Fig. 3
a Schistosomula in 10 µg/ml PVS showing absence of the black pigmentation of the gut (×4 objective). b Schistosomula in 1 µg/ml PZQ showing the black pigmentation of the gut (×4 objective)
Fig. 4
Fig. 4
Bar chart illustrating mean total worm burden among different study groups. A decrease in mean total worm burden in each of subgroup a in groups I, II, III and IV in comparison to group V was recorded. Subgroup a in group I showed decrease in mean number of worms than subgroup b of the same group
Fig. 5
Fig. 5
Bar chart illustrating mean egg count/gm intestine among different study groups. A decrease in mean egg count/gm intestine in subgroup a of groups I, II, III and IV compared to group V was recorded. Subgroup a in each of group III and IV showed decrease in mean egg count than subgroup b of same groups
Fig. 6
Fig. 6
Bar chart illustrating mean count of eggs/gm liver among different study groups showing a decrease in subgroup a in each of groups I, II, III and IV in comparison to group V
Fig. 7
Fig. 7
Hepatic granuloma in groups of study. a Subgroup IIa showing a single dead partially calcified S. mansoni ova in the center of a well circumscribed granuloma made up of fibroblasts with lymphocytes mainly seen at the periphery. Perigranulomatous tissue shows expansion of portal tracts by lymphocytic infiltrate along with bile duct injury and focal interface hepatocytes (Hx and E stain ×400). b Subgroup IIb showing a single dead partially calcified S. mansoni ova in the center of a partially circumscribed granuloma made up of histiocytes and fibroblasts with intervening collagen, lymphocytes mainly seen at the periphery (Hx and E stain ×400). c Infection control group (V) showing granuloma made up of histiocytes and few fibroblasts with lymphocytes mainly the periphery, a viable S. mansoni ova is seen, perigranulomatous tissue shows lymphocytic infiltrate along with bilharzial pigment in Von-Kupffer cells (Hx and E stain ×400). d Normal control group (VI) (Hx and E stain ×400)
Fig. 8
Fig. 8
Bar chart illustrating mean hepatic granuloma number among different study groups showing a decrease in mean hepatic granuloma number in subgroup a of each of group I, II, III and IV compared to group V
Fig. 9
Fig. 9
Bar chart illustrating mean hepatic granuloma size among different study groups. A decrease in mean hepatic granuloma size in subgroup a of each of group I, II, III and IV compared to group V, and compared to subgroup b of the same groups
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