Potential i‐Nos/Arg‐1 Switch with NLRP3 and Parasitic Load Down Regulation in Experimental Schistosoma mansoni Infection via Chloroquine Repurposing

ABSTRACT In previous studies, the inhibitory effect of chloroquine on NLRP3 inflammasome and heme production was documented. This may be employed as a double‐bladed sword in schistosomiasis (anti‐inflammatory and parasiticidal). In this study, chloroquine's impact on schistosomiasis mansoni was...

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Published in:Parasite immunology 2024-03, Vol.46 (3), p.e13030-n/a
Main Authors: Hasby Saad, Marwa A., El‐Saadi, Esraa G., Ali, Dareen A., Watany, Mona M., Eid, Mohammed M.
Format: Article
Language:English
Subjects:
Animals
Chloroquine
Chloroquine - pharmacology
Down-Regulation
Drug Repositioning
Fibrosis
hepatic fibrosis
Immunological tolerance
Inflammasomes
Inflammation
i‐Nos/Arg‐1
Liver
Macrophages
Mice
NLR Family, Pyrin Domain-Containing 3 Protein - genetics
NLRP3 inflammasome
Parasite Load
Polarization
Praziquantel
Praziquantel - pharmacology
Rodent Diseases
S. mansoni
Schistosomiasis
Schistosomiasis mansoni - drug therapy
Spleen
Splenomegaly
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Summary:ABSTRACT In previous studies, the inhibitory effect of chloroquine on NLRP3 inflammasome and heme production was documented. This may be employed as a double‐bladed sword in schistosomiasis (anti‐inflammatory and parasiticidal). In this study, chloroquine's impact on schistosomiasis mansoni was investigated. The parasitic load (worm/egg counts and reproductive capacity index [RCI]), i‐Nos/Arg‐1 expression, splenomegaly, hepatic insult and NLRP3‐immunohistochemical expression were assessed in infected mice after receiving early and late repeated doses of chloroquine alone or dually with praziquantel. By early treatment, the least RCI was reported in dually treated mice (41.48 ± 28.58) with a significant reduction in worm/egg counts (3.50 ± 1.29/2550 ± 479.58), compared with either drug alone. A marked reduction in the splenic index was achieved by prolonged chloroquine administration (alone: 43.15 ± 5.67, dually: 36.03 ± 5.27), with significantly less fibrosis (15 ± 3.37, 14.25 ± 2.22) than after praziquantel alone (20.5 ± 2.65). Regarding inflammation, despite the praziquantel‐induced significant decrease in NLRP3 expression, the inhibitory effect was marked after dual and chloroquine administration (liver: 3.13 ± 1.21/3.45 ± 1.23, spleen: 5.7 ± 1.6/4.63 ± 2.41). i‐Nos RNA peaked with early/late chloroquine administration (liver: 68.53 ± 1.8/57.78 ± 7.14, spleen: 63.22 ± 2.06/62.5 ± 3.05). High i‐Nos echoed with a parasiticidal and hepatoprotective effect and may indicate macrophage‐1 polarisation. On the flip side, the chloroquine‐induced low Arg‐1 seemed to abate immune tolerance and probably macrophage‐2 polarisation. Collectively, chloroquine synergised the praziquantel‐schistosomicidal effect and minimised tissue inflammation, splenomegaly and hepatic fibrosis.
ISSN:0141-9838
1365-3024
DOI:10.1111/pim.13030