Murine Schistosomiasis Mansoni Research Articles

Differential protective impact of peptide vaccine formulae targeting the lung- and liver-stage of challenge Schistosoma mansoni infection in mice

The study aimed to elicit protective immune responses against murine schistosomiasis mansoni at the parasite lung- and liver stage. Two peptides showing amino acid sequence similarity to gut cysteine peptidases, which induce strong memory immune effectors in the liver, were combined with a peptide based on S. mansoni thioredoxin peroxidase (TPX), a prominent lung-stage schistosomula excretory-secretory product, and alum as adjuvant. Only one of the 2 cysteine peptidases-based peptides in a multiple antigenic peptide construct (MAP-3 and MAP-4) appeared to adjuvant protective immune responses induced by the TPX peptide in a MAP form. Production of TPX MAP-specific IgG1 serum antibodies, and increase in lung interleukin-1 (IL-1), uric acid, and reactive oxygen species (ROS) content were associated with significant (P < 0.05) 50 % reduction in recovery of lung-stage larvae. Increase in lung triglycerides and cholesterol levels appeared to provide the surviving worms with nutrients necessary for a stout double lipid bilayer barrier at the parasite-host interface. Surviving worms-released products elicited memory responses to the MAP-3 immunogen, including production of specific IgG1 antibodies and increase in liver IL-33 and ROS. Reduction in challenge worm burden recorded 45 days post infection did not exceed 48 % associated with no differences in parasite egg counts in the host liver and small intestine compared to unimmunized adjuvant control mice. Alum adjuvant assisted the second peptide, MAP-4, in production of IgG1, IgG2a, IgG2b and IgA specific antibodies and increase in liver ROS, but with no protective potential, raising doubt about the necessity of adjuvant addition. Accordingly, different vaccine formulas containing TPX MAP and 1, 2 or 3 cysteine peptidases-derived peptides with or without alum were used to immunize parallel groups of mice. Compared to unimmunized control mice, significant (P < 0.05 to < 0.005) 22 to 54 % reduction in worm burden was recorded in the different groups associated with insignificant changes in parasite egg output. The results together indicated that a schistosomiasis vaccine able to entirely prevent disease and halt its transmission still remains elusive.

Evaluation of schistosomula lung antigen preparation and soluble egg antigen vaccines on experimental schistosomiasis mansoni.

Schistosomiasis causes significant morbidity and mortality worldwide. This study aimed to assess the effect of schistosomula lung antigen preparation (SLAP) and soluble egg antigen (SEA) on a murine schistosomiasis mansoni model. Ninety laboratory-bred male Swiss albino mice were divided into 6 groups. Two doses of the vaccine were given at 2-week intervals. All mice were subcutaneously infected with 80±10 Schistosoma mansoni cercariae 2 weeks after the last vaccination dose. They were sacrificed 7 weeks post-infection. Parasitological and histopathological studies were conducted to assess the effect of inoculated antigens (single or combined). The results showed that the combination of SLAP and SEA (combination group) led to a significant reduction in worm burden (65.56%), and liver and intestine egg count (59% and 60.59%, respectively). The oogram pattern revealed a reduction in immature and mature eggs (15±0.4 and 10±0.8, respectively) and an increased number of dead eggs in the combination group (P<0.001). In terms of histopathological changes, the combination group showed notably small compact fibrocellular egg granuloma and moderate fibrosis in the liver. A high percentage of destroyed ova was observed in the intestine of the combination group. This study demonstrates for the first time the prophylactic effect of combined SLAP and SEA vaccine. The vaccine induced a significant reduction in the parasitological and pathological impacts of schistosomiasis mansoni in hepatic and intestinal tissues, making it a promising vaccine candidate for controlling schistosomiasis.

Rutin, a Flavonoid Compound Derived from Garlic, as a Potential Immunomodulatory and Anti-Inflammatory Agent against Murine Schistosomiasis mansoni.

Schistosomiasis is a tropical disease caused by trematode worms. The inflammatory response of the host to schistosome eggs leads to formation of granuloma in the liver and intestine. Praziquantel (PZQ) is still an effective treatment for schistosomiasis, however resistance development may reduce its efficacy. The current study investigated the possible immunomodulatory and anti-inflammatory action of rutin, a natural flavonoid compound isolated from garlic, on liver fibrotic markers in mice infected with S. mansoni in comparison to PZQ. Male albino CD1 mice were infected with 100 ± 2 S. mansoni cercariae/mouse and treated with garlic, rutin, or PZQ. At the end of the experiment, the liver and intestines were harvested for parasitological and histological assessment and to analyze the proinflammatory cytokine. Rutin significantly affects the pathological alterations caused by Schistosoma in the liver. This may be partially explained by a decrease in the number of eggs trapped in the tissues of the liver and a modification in the serum levels of certain cytokines, which are implicated in the formation of Schistosoma granuloma. In conclusion, rutin has strong anti-schistosome properties in vivo, raising the possibility that rutin might be further investigated as a therapy for S. mansoni.

Cholagogue Additive Effect of Ursodeoxycholic acid to Praziquantel on murine Schistosomiasis mansoni: Parasitological and Histopathological studies

Cholagogue Additive Effect of Ursodeoxycholic acid to Praziquantel on murine Schistosomiasis mansoni: Parasitological and Histopathological studies

Juglone: "A novel immunomodulatory, antifibrotic, and schistosomicidal agent to ameliorate liver damage in murine schistosomiasis mansoni".

Schistosomiasis remains one of the world's leading health concerns, affecting millions. The granulomatous reaction is the most significant immunopathological change associated with Schistosoma mansoni infection, resulting in significant mortality. Recent progress has been made in the search for new natural compounds to reduce schistosomiasis and its immunopathology. Walnuts contain the phenolic compound Juglone (5-hydroxy-1,4-naphthoquinone), which has antiparasitic, anti-inflammatory, immunoregulatory, and antioxidant properties. There were three groups of infected mice: untreated (IU), Juglone-treated (JUG T), and praziquantel-treated (PZ). In mice treated at 8mg Juglone /kg body weight, a reduction of 63.1% and 52.1% were observed in the number of male and female worms, respectively. In addition, the number of eggs/g tissue was reduced by 65.7% in the liver, 58.58% in the intestine, and 62.31% in the liver and intestine combined. In addition, Juglone decreased hepatic granuloma size by 55.1% and collagen fiber deposition by 23.4% compared to PZQ (41.18% and 11.2%, respectively). Interestingly, the JUG T group had significantly lower levels of IL-4, IL-13, IL-37, TNF-α, TGF-β, and IFN-γ than PZ mice (p<0.05). While IL-10 and IL-17 levels rose (p<0.01), Juglone could restore hepatic ALT, AST, GGT, and LDH activities following infection. In addition, it increased catalase, SOD, GSH, and GST while decreasing NO and LPO in comparison to the infected group. Moreover, anti-SWAP, SEA, and CAP IgG levels increased significantly. IgE levels did not change significantly, however. Juglone could be used as an antifibrotic, immunomodulatory, and schistosomicidal agent; thus, it could be used in place of PZQ.

Expression of microRNA-223 and microRNA-146b in serum and liver tissue of mice infected with Schistosoma mansoni

MicroRNAs (miRNAs) play regulatory roles in several diseases. In schistosomiasis, the main pathological changes are caused by the granulomatous reaction induced by egg deposition. We aimed to study the changes in host miRNA-223 and miRNA-146b expression in relation to egg deposition and development of hepatic pathology in murine schistosomiasis mansoni. Blood and liver tissue samples were collected from non-infected mice (group I), S. mansoni–infected mice at the 4th, 8th, and 12th weeks post-infection (p.i.) (groups II–IV), and 4 weeks after praziquantel treatment (group V). The collected samples were processed for RNA extraction, reverse transcription, and real-time PCR analysis of miRNA-223 and miRNA-146b. miRNAs’ relative expression was estimated by the ΔΔCt method. Liver tissue samples were examined for egg count estimation and histopathological evaluation. Results revealed that miRNA-223 was significantly downregulated in liver tissues 8 and 12 weeks p.i., whereas miRNA-146b expression increased gradually with the progression of infection with a significantly higher level at week 12 p.i. compared to week 4 p.i. Serum expression levels nearly followed the same pattern as the tissue levels. The dysregulated expression of miRNAs correlated with liver egg counts and was more obvious with the demonstration of chronic granulomas, fibrous transformation, and distorted hepatic architecture 12 weeks p.i. Restoration of normal expression levels was observed 4 weeks after treatment. Collectively, these findings provide new insights for in-depth understanding of host-parasite interaction in schistosomiasis and pave a new way for monitoring the progress of hepatic pathology before and after treatment.

Schistosoma mansoni egg-derived extracellular vesicles: A promising vaccine candidate against murine schistosomiasis.

Extracellular vesicles (EVs) are protein-loaded nano-scaled particles that are extracellularly released by eukaryotes and prokaryotes. Parasite’s EVs manipulate the immune system, making them probable next-generation vaccines. Schistosomal EVs carry different proteins of promising immunizing potentials. For evaluating the immune-protective role of Schistosoma mansoni (S. mansoni) egg-derived EVs against murine schistosomiasis, EVs were isolated from cultured S. mansoni eggs by progressive sequential cooling ultra-centrifugation technique. Isolated EVs were structurally identified using transmission electron microscope and their protein was quantified by Lowry’s technique. Experimental mice were subcutaneously immunized with three doses of 20 μg EVs (with or without alum adjuvant); every two weeks, then were challenged with S. mansoni cercariae two weeks after the last immunizing dose. Six weeks post infection, mice were sacrificed for vaccine candidate assessment. EVs protective efficacy was evaluated through parasitological, histopathological, and immunological parameters. Results showed significant reduction of tegumentally deranged adult worms, hepatic and intestinal egg counts reduction by 46.58%, 93.14% and 93.17% respectively, accompanied by remarkable amelioration of sizes, numbers and histopathology of hepatic granulomata mediated by high interferon gamma (IFN γ) and antibody level. Using sera from vaccinated mice, the molecular weight of EVs’ protein components targeted by the antibody produced was recognized by western immunoblot. Results revealed two bands of ~ 14 KDa and ~ 21 KDa, proving that EVs are able to stimulate specific antibodies response. In conclusion, the present study highlighted the role of S. mansoni-egg derived EVs as a potential vaccine candidate against murine schistosomiasis mansoni.

Regulation of Liver Fibrosis during Murine Schistosomiasis Mansoni

Background: The main pathology of Schistosoma mansoni (S. mansoni) infection is induced by a granulomatous tissue reaction against the parasite eggs. Unfortunately, no therapy has been proven to prevent the progression of hepatic fibrosis associated with granulomatous hypersensitivity to parasite eggs. Accumulating evidence has demonstrated a critical pathogenic role for both interleukin 17 (IL-17) and interleukin 13 (IL-13) in organ fibrosis. Objective: The present study investigated the role of IL-17 and IL-13 in the pathogenesis of liver fibrosis during S. mansoni infection. Material and Methods: Thirty female C57BL/6 mice were divided into three groups, normal, infected, and anti- mouse IL-17 treated groups. The infected and anti-mouse IL-17 groups were infected with 40±5 cercariae of S. mansoni per mouse. Neutralizing rat anti-mouse IL-17 mAb or an isotype-matched rat IgG mAb was first administered intraperitoneally 3 weeks after S. mansoni infection (62.5μg per mouse) then at the same dose every third day until 2 days before killing. Serum IL-17, IL-13, and proinflammatory cytokines levels were determined by ELISA. Liver granulomas were measured by an ocular micrometer. Results: Serum level of IL-17 was significantly higher in infected mice compared with non-infected animals. Reducing IL-17 activity using anti-IL-17 monoclonal antibodies improves liver functions and reduces the size of the liver granulomas. Meanwhile, Th-2 profibrogenic cytokine IL-13 was also decreased in infected/anti-IL-17 mAB- treated mice. IL-17-induced proinflammatory mediators (IL-1Land TNF-that involved in liver fibrosis were markedly reduced in anti-IL-17 mAB-treated mice. Conclusion: IL-17 and IL-13 contribute to granulomatous inflammatory and fibrosing reactions in murine schistosomiasis.

Regulation of Liver Fibrosis during Murine Schistosomiasis Mansoni

Background: The main pathology of Schistosoma mansoni (S. mansoni) infection is induced by a granulomatous tissue reaction against the parasite eggs. Unfortunately, no therapy has been proven to prevent the progression of hepatic fibrosis associated with granulomatous hypersensitivity to parasite eggs. Accumulating evidence has demonstrated a critical pathogenic role for both interleukin 17 (IL-17) and interleukin 13 (IL-13) in organ fibrosis. Objective: The present study investigated the role of IL-17 and IL-13 in the pathogenesis of liver fibrosis during S. mansoni infection. Material and Methods: Thirty female C57BL/6 mice were divided into three groups, normal, infected, and anti- mouse IL-17 treated groups. The infected and anti-mouse IL-17 groups were infected with 40±5 cercariae of S. mansoni per mouse. Neutralizing rat anti-mouse IL-17 mAb or an isotype-matched rat IgG mAb was first administered intraperitoneally 3 weeks after S. mansoni infection (62.5μg per mouse) then at the same dose every third day until 2 days before killing. Serum IL-17, IL-13, and proinflammatory cytokines levels were determined by ELISA. Liver granulomas were measured by an ocular micrometer. Results: Serum level of IL-17 was significantly higher in infected mice compared with non-infected animals. Reducing IL-17 activity using anti-IL-17 monoclonal antibodies improves liver functions and reduces the size of the liver granulomas. Meanwhile, Th-2 profibrogenic cytokine IL-13 was also decreased in infected/anti-IL-17 mAB- treated mice. IL-17-induced proinflammatory mediators (IL-1Land TNF-that involved in liver fibrosis were markedly reduced in anti-IL-17 mAB-treated mice. Conclusion: IL-17 and IL-13 contribute to granulomatous inflammatory and fibrosing reactions in murine schistosomiasis.

Single oral fixed-dose praziquantel-miltefosine nanocombination for effective control of experimental schistosomiasis mansoni

BackgroundThe control of schistosomiasis has been centered to date on a single drug, praziquantel, with shortcomings including treatment failure, reinfection, and emergence of drug resistance. Drug repurposing, combination therapy or nanotechnology were explored to improve antischistosomal treatment. The aim of the present study was to utilize a novel combination of the three strategies to improve the therapeutic profile of praziquantel. This was based on a fixed-dose nanocombination of praziquantel and miltefosine, an antischistosomal repurposing candidate, co-loaded at reduced doses into lipid nanocapsules, for single dose oral therapy.MethodsTwo nanocombinations were prepared to provide 250 mg praziquantel-20 mg miltefosine/kg (higher fixed-dose) or 125 mg praziquantel-10 mg miltefosine/kg (lower fixed-dose), respectively. Their antischistosomal efficacy in comparison with a non-treated control and their praziquantel or miltefosine singly loaded counterparts was assessed in murine schistosomiasis mansoni. A single oral dose of either formulation was administered on the initial day of infection, and on days 21 and 42 post-infection. Scanning electron microscopic, parasitological, and histopathological studies were used for assessment. Preclinical data were subjected to analysis of variance and Tukeyʼs post-hoc test for pairwise comparisons.ResultsLipid nanocapsules (~ 58 nm) showed high entrapment efficiency of both drugs (> 97%). Compared to singly loaded praziquantel-lipid nanocapsules, the higher nanocombination dose showed a significant increase in antischistosomal efficacy in terms of statistically significant decrease in mean worm burden, particularly against invasive and juvenile worms, and amelioration of hepatic granulomas (P ≤ 0.05). In addition, scanning electron microscopy examination showed extensive dorsal tegumental damage with noticeable deposition of nanostructures.ConclusionsThe therapeutic profile of praziquantel could be improved by a novel multiple approach integrating drug repurposing, combination therapy and nanotechnology. Multistage activity and amelioration of liver pathology could be achieved by a new praziquantel-miltefosine fixed-dose nanocombination providing 250 mg praziquantel-20 mg miltefosine/kg. To the best of our knowledge, this is the first report of a fixed-dose nano-based combinatorial therapy for schistosomiasis mansoni. Further studies are needed to document the nanocombination safety and explore its prophylactic activity and potential to hinder the onset of resistance to the drug components.

Cell therapy as a new approach on hepatic fibrosis of murine model of Schistosoma mansoni-infection.

Schistosomiasis is an acute and chronic disease of the genus Schistosoma triggered by blood flukes. Schistosomiasis is a disease occurring in, or endemic to, tropical and subtropical regions. A new concept was implemented to deal with schistosomiasis from natural plant sources. Curcumin's common name is Turmeric. Curcumin has proven to be main active component in Curcuma longa L. and has a wide range of anti-phrastic effects. Previous studies have shown the role of bone marrow mesenchymal stem cells (BMSCs) therapy in hepatic fibrosis recovery. The current study was, therefore, intended to examine therapeutic role of BMSCs and Turmeric in murine schistosomiasis mansoni. Mice were divided into five groups: a negative control group (non-infected non-treated), a positive control group (infected non-treated), a BMSCs treated group; Turmeric treated group, and untreated group. BMSCs derived from male mice were injected intraperitoneally into female mice receiving S. mansoni cercariae through the subcutaneous route. Liver histopathology and immuno-histochemical examinations were evaluated. BMSCs intraperitoneal injection resulted in a significant reduction of liver collagen, granuloma size, and significant increase of OV-6 expression in the Schistosomiasis-treated mice group. There was overall improvement in pathological changes of the liver. Unfortunately, group IV showed a mild improvement in the granuloma size and fibrosis compared to corresponding BMSCs treatment group, although with vacuolated liver cells. BMSCs have a regenerative potential in liver tissue histopathology by decreasing liver fibrosis and granulomas. Turmeric, by contrast, could not be used as an anti-fibrotic, according to the findings.

Effect of a newly synthesized quinoline-based compound (PPQ-8) on murine schistosomiasis mansoni.

Schistosomiasis represents a public health problem and praziquantel is the only drug used for treatment of all forms of the disease. Thus, the development of new anti-schistosomal agents is of utmost importance to increase the effectiveness, reduce side effects and delay the emergence of resistance. The present study was conducted to report the therapeutic efficacy of PPQ-8, a new synthetic quinoline-based compound against Schistosoma mansoni. Mice were treated with PPQ-8 at day 49 post infection using two treatment regimens (20 and 40 mg/kg). Significant reductions were recorded in hepatic (62.9% and 83.6%) and intestinal tissue egg load (57.4% and 73.5%), granuloma count (75.4% and 89.1%) and diameter (26.2% and 47.3%), in response to the drug regimens, respectively. In addition, both treatment regimens induced significant decrease in liver (23.3% and 32.8%) and spleen (37.5% and 45.3%) indices. Also, there were significant reductions in mature ova, total worm and female count, which were more prominent with the higher dose. The reduction in the level of nitric oxide in the liver by both therapeutic regimens to 22.5% and 47.2% indicates the anti-oxidant activity of PPQ-8. Bright field microscopic examination of worms recovered from infected and PPQ-8-treated mice showed nearly empty intestinal caeca with no observable changes in the tegument. Our findings hold promise for the development of a novel anti-schistosomal drug using PPQ-8, but further in vitro and in vivo studies are needed to elucidate the possible mechanism/s of action and to study the effect of PPQ-8 on other human schistosomes.

Therapeutic efficacy of a newly synthesized benzimidazole compound BTP-OH against murine schistosomiasis mansoni.

Because of the increasingly emerging praziquantel resistance, there is a crucial need to develop new anti-schistosomal agents. This work was conducted to assess the therapeutic efficacy of a new benzimidazole compound (BTP-OH) in mice experimentally infected with Schistosoma mansoni. A total of 40 Swiss albino female mice were divided into an infected untreated group and three infected treated groups (using praziquantel and BTP-OH). The compound activity was evaluated through parasitological, histopathological and scanning electron microscopy studies. Praziquantel and BTP-OH at both doses significantly reduced male (75%, 42.67% and 61.08%, respectively), female (71.45%, 48.94% and 68.13%, respectively) and total worm burden (75.21%, 42.42% and 62.28%, respectively), as well as tissue egg load in the liver (71.22%, 42.12% and 66.04%, respectively). In oogram, praziquantel significantly increased the percentage of dead eggs (65.89%), while BTP-OH significantly reduced the percentage of immature eggs (30.43% and 19.64%). BTP-OH significantly diminished granuloma count (33.87% and 44.77%) and diameter (39.23% and 49.40%), and caused ultrastructural changes in the tegument of adult schistosomes. This study provides evidence for the schistosomicidal efficacy of BTP-OH. However, future studies are needed to elucidate the full mechanisms of action and effects of BTP-OH on other human schistosomes.

Urinary circulating DNA and circulating antigen for diagnosis of schistosomiasis mansoni: a field study.

To evaluate three non-invasive assays for the diagnosis of schistosomiasis mansoni in an Egyptian village. Urine was collected for the detection of circulating cathodic antigen (CCA) and cell-free parasite DNA (cfpd) by Point-of-contact (POC)-cassette assay and PCR, respectively. These tests were compared to Kato-Katz (KK) faecal thick smear for detection of Schistosoma mansoni eggs. Disease prevalence by POC-CCA assay was 86%; by PCR it was 39% vs. 27% by KK. Compared to KK, the sensitivity of POC-CCA reached 100%, but its specificity was only 19.2% with 41% accuracy. Sensitivity of the PCR assay for cfpd was 55.56%, and specificity was 67.12% with 64% accuracy. A new end point was calculated for combined analysis of KK, POC-CCA assay and PCR. Sensitivity for the three tests was 52.94%, 90.2% and 76.47%; specificity was 100% for KK and PCR and 18.37% for POC-CCA. The accuracy calculated for the three tests at the end point was 76% for KK, 55% for POC-CCA assay and 88% for PCR. Conventional PCR assay for detection of cfpd provides a potential screening tool for intestinal schistosomiasis with reliable specificity, reasonable accuracy and affordable financial and technical cost.

Therapeutic potential effect of bone marrow-derived mesenchymal stem cells on chronic liver disease in murine Schistosomiasis Mansoni.

Some reports have shown that mesenchymal stem cells (MSCs) therapy could ameliorate chemically-induced hepatic fibrosis. This research assesses the therapeutic action of bone marrow mesenchymal stem cells (BM-MSCs) on chronic diseased liver in Schistosoma mansoni infected mice. All infected female mice divided into three groups, one group (15 mice) treated with oral praziquantel (PZQ), second group (15 mice) received intravenous injection of BM-MSCs and third group (15 mice) treated with both MSCs + PZQ. Two control groups (15 mice each) subdivided into one infected and second healthy one. BM-MSCs were obtained from bones of both femur and tibia of male mice (30 mice), then cultured and characterized morphologically by detection of CD105 by flow cytometer. Liver tissues for all groups were examined histopathologically. Measuring of the collagen 1 gene expression was done by real-time PCR and immunohistochemical study to detect stem cells differentiation for detection of MSCs engraftments in liver tissue. MSCs treatment caused marked improvement and regression of fibrosis, and prevents deposition of collagen and reduced the expression of collagen 1 gene in infected mice on their liver tissues, especially when used with PZQ in mice treatment. It can be concluded that, MSCs is a good therapeutic method for liver fibrosis caused by S. mansoni infection.

HPLC-ESI-MS Characterization of Certain Polyphenolic Compounds of Carica papaya L. Fruit Extracts and Evaluation of Their Potential Against Murine Schistosomiasis mansoni.

The in vivo antischistosomal activities of Carica papaya L. extracts were evaluated and the characterization of the active secondary metabolites of the defatted methanolic extract was performed using HPLC-ESI-MS. The plant fruit powders were extracted with 85% methanol and fractionated using organic solvents. The in vivo antischistosomal effects of the methanolic extracts and its fractions, as well as the assessment of the relationship between the antischistosomal activity of these plant extracts and oxidative stress, was determined. In addition, the defatted methanolic extract was characterized by HPLC-ESI-MS analysis. The number of worms, ova, and the Oogram pattern displayed typical Schistosoma mansoni pathology 8 weeks after infection in mice. Treatment of the infected group with the defatted methanolic extracts significantly decreased worm burden, immature ova and mature ova, while increasing the percentage of dead ova in vivo. The butanol fraction was the most effective fraction reducing worm burden by 77%, ova count in the intestine by 76% and in the liver by 80%, and significantly decreased immature and mature ova (P<0.001) compared to the infected group. Additionally, the defatted methanolic extracts improved the reduced glutathione and malondialdehyde levels in hepatic tissues in the treated groups compared to the infected group. The HPLC-ESI-MS analysis of the Carica papaya defatted methanolic extract revealed the presence of several polyphenolic compounds. Carica papaya fruit extracts are rich with phenolic acids and flavonoids and show a significant effect against S. mansoni infections which may be used alternative to PZQ as anti-schistosomal drug against schistosomiasis.

Paeoniflorin targets apoptosis and ameliorates fibrosis in murine schistosomiasis mansoni: A novel insight

Schistosomiasis is a chronic helminthic disease causing hepatic fibrosis. Some studies demonstrated direct effect of targeting apoptosis on fibrosis regression. This study is a novel trial of Paeoniflorin (PAE) on S. mansoni induced hepatic fibrosis in murine model compared to Praziquantel (PZQ) evaluating their anti-parasitic and anti-fibrotic properties aiming to discover a new therapy that decrease schistosomiasis morbidity. Thirty two laboratory bred Swiss albino male CD-1 mice were used in this study. The mice were classified into four groups (8 mice each), control healthy, control infected, PZQ treated (300 mg/kg/12 h), PAE treated (50 mg/kg/d) groups. All mice groups were sacrificed 15 weeks post infection for assessment of drugs efficacy by parasitological, histopathological, immunohistochemical and serological studies. Our results showed that PAE improved the parasitological parameters including decrease worm burden, immature, mature eggs and increase dead ones yet, still PZQ had the upper hand in this aspect. However, PAE exceeded PZQ as an anti-fibrotic therapy seemed in marked decrease in hepatic mean granuloma diameter and fibrosis area, besides, marked increase in serum tumor necrosis factor-alpha; TNF-α level, caspase-3 and P53 apoptotic expressions. There was marked decrease in serum IL-13 level, nuclear factor-kappa B; NF-kB, Transforming Growth Factor-Beta1; TGF-β1, Alpha-Smooth Muscle Actin; α-SMA fibrotic expressions. Conclusively, PAE could be an anti schistosomiasis mansoni therapy exceeding PZQ in targeting apoptosis and ameliorating fibrosis. This study provides a perspective for a novel therapeutic approach to prevent liver fibrosis following liver injury due to schistosomiasis mansoni.

Efficacy of soluble glycoprotein fraction from Allium sativum purified by size exclusion chromatography on murine Schistosomiasis mansoni.

In this work, the efficiency of crude MeOH extracts and soluble glycoprotein fraction of Allium sativum purified by size-exclusion chromatography (SEC) on parasitological, histopathological and some biochemical parameters in Schistosoma mansoni infected mice were investigated. Animals were infected by tail immersion with 100 cercariae/each mouse and divided into five groups in addition to the normal control. The results revealed a significant decrease in mean worm burden in all treated mice especially in the group treated with soluble glycoprotein fraction of A.sativum as compared to infected non-treated control with the disappearance of female worms. Administration of the studied extracts revealed remarkable amelioration in the levels of all the measured parameters in S.mansoni infected mice. In addition, treatment of mice with crude A.sativum MeOH extract and soluble glycoprotein fraction of A.sativum decreased significantly the activities of studied enzymes as compared to the infected untreated group. The highest degrees of enhancement in pathological changes was observed in the treated one with soluble glycoprotein fraction of A.sativum compared to the infected group represented by small sized, late fibro-cellular granuloma, the decrease in cellular constituents and degenerative changes in eggs. In conclusion, A.sativum treatment had effective schistosomicidal activities, through reduction of worm burden and tissue eggs, especially when it was given in purified glycoprotein fraction. Moreover, the soluble glycoprotein fraction of A.sativum largely modulates both the size and the number of granulomas.

Osteopontin Is Upregulated in Human and Murine Acute Schistosomiasis Mansoni.

BackgroundSymptomatic acute schistosomiasis mansoni is a systemic hypersensitivity reaction against the migrating schistosomula and mature eggs after a primary infection. The mechanisms involved in the pathogenesis of acute schistosomiasis are not fully elucidated. Osteopontin has been implicated in granulomatous reactions and in acute hepatic injury. Our aims were to evaluate if osteopontin plays a role in acute Schistosoma mansoni infection in both human and experimentally infected mice and if circulating OPN levels could be a novel biomarker of this infection.Methodology/Principal FindingsSerum/plasma osteopontin levels were measured by ELISA in patients with acute (n = 28), hepatointestinal (n = 26), hepatosplenic (n = 39) schistosomiasis and in uninfected controls (n = 21). Liver osteopontin was assessed by immunohistochemistry in needle biopsies of 5 patients. Sera and hepatic osteopontin were quantified in the murine model of schistosomiasis mansoni during acute (7 and 8 weeks post infection, n = 10) and chronic (30 weeks post infection, n = 8) phase. Circulating osteopontin levels are increased in patients with acute schistosomiasis (p = 0.0001). The highest levels of OPN were observed during the peak of clinical symptoms (7–11 weeks post infection), returning to baseline level once the granulomas were modulated (>12 weeks post infection). The plasma levels in acute schistosomiasis were even higher than in hepatosplenic patients. The murine model mirrored the human disease. Macrophages were the major source of OPN in human and murine acute schistosomiasis, while the ductular reaction maintains OPN production in hepatosplenic disease. Soluble egg antigens from S. mansoni induced OPN expression in primary human kupffer cells.Conclusions/SignificanceS. mansoni egg antigens induce the production of OPN by macrophages in the necrotic-exudative granulomas characteristic of acute schistosomiasis mansoni. Circulating OPN levels are upregulated in human and murine acute schistosomiasis and could be a non-invasive biomarker of this form of disease.

Serum osteopontin is a biomarker of severe fibrosis and portal hypertension in human and murine schistosomiasis mansoni

Schistosomiasis is a major cause of fibrosis and portal hypertension. The reason 4–10% of infected subjects develops hepatosplenic schistosomiasis remains unclear. Chronically infected male CBA/J mice reproduce the dichotomic forms of human schistosomiasis. Most mice (80%) develop moderate splenomegaly syndrome (similar to hepatointestinal disease in humans) and 20% present severe hypersplenomegaly syndrome (analogous to human hepatosplenic disease). We demonstrated that the profibrogenic molecule osteopontin discriminates between mice with severe and mild disease and could be a novel morbidity biomarker in murine and human schistosomiasis. Failure to downregulate osteopontin during the chronic phase may explain why hepatosplenic subjects develop severe fibrosis.