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Reversal of Liver Fibrosis in Chronic Murine Schistosomiasis mansoni by Safironil/Praziquantel
NO Al-Harbi, SA Bahashwan, MS Aboonq, MA Ramadan, AA Bahashwan
Tropical Journal of Pharmaceutical Research , 2012,
Abstract: Purpose: To evaluate the safety, pharmacological effect and mechanism of action of an antifibrotic compound, safironil (SAF)/praziquantel (PZQ) combination on reversal of liver fibrogenesis in chronic murine Schistosomiasis mansoni. Methods: The antifibrotic effect of 0.5, 1 and 2 mg/ml of SAF was evaluated in vitro myofibroblast cell culture, using RNAse protection assay for collagen I mRNA expression and quantitative immunoblot for smooth muscle α-actin protein extract. Ninety Swiss albino mice were infected with 50 Schistosoma mansoni cercariae. SAF was provided in drinking water at a concentration of 1.5 mg/ml while praziquantel (PZQ) was given by gavage in a dose of 500 mg/kg. Mice, divided into five groups: infected non-treated; infected and PZQ-treated; infected PZQ- and SAF-treated; infected and SAF-treated; and control. After sacrificing the animals, the liver of each mouse was taken, weighed and used for histopathological examination, hydroxyproline assay and collagen determination. Results: SAF prevented myofibroblast activation at the pre-transcriptional level in a dose-dependent manner as monitored by collagen I mRNA levels (expression reduced by 40, 70 and 90 % at doses of 0.5, 1 and 2 mg/ml, respectively) or by smooth muscle α-actin (expression reduced by 70, 85 and 95 %, respectively). SAF decreased the production of collagen I by 60 % and laminin by 55 % but increased collagen III by 50 % relative to control. SAF had no effect on liver granuloma size and did not alter total hydroxyproline but altered the pattern of fibrosis by increasing collagen III and decreasing collagen I deposition. The most significant reduction in liver fibrosis was noticed in mice treated with SAF combined with PZQ. No toxic pharmacological effect was noticed during SAF treatment. Conclusion: When SAF was combined with PZQ, augmented reduction of liver fibrogenesis was achieved. The mechanism is probably through inhibition of new liver injury induced by parasite egg deposition and interruption of collagen type I synthesis with attenuation of pre-existent collagen.
Immunohistochemical expression of oestrogen and progesterone receptors during experimental acute and chronic murine Schistosomiasis mansoni
Habib, Fawzia Ahmed;Zaki, Mayssa Mohamed;El-Aal, Amany Ahmed Abd;Safwat, Maha Dia Eldean;Domiaty, Magda Ahmed El;
Revista da Sociedade Brasileira de Medicina Tropical , 2010, DOI: 10.1590/S0037-86822010000500012
Abstract: introduction: the responsibility of schistosoma mansoni in female infertility is still controversial. this study was conducted to evaluate the effect of acute and chronic schistosomiasis mansoni infection on the endometrium using immunohistochemical analysis of uterine hormone receptor expression. methods: twenty-four nonpregnant swiss albino mice were divided into three groups: control, noninfected; acute; and chronic schistosoma mansoni infection. histological sections of uterine specimens were examined by light microscope with an image analyzing system to detect structural histological, estrogen receptor (er) and progesterone receptor (pr) expression in the endometrium. results: no secretory phase was detected in the endometrium in acute and chronic schistosoma infection. hormone receptor expression (er and pr) showed statistically significant differences among the groups (p< 0.05), with significant low er hormone expression in chronic infection, compared to control proliferative, control secretory and acute infection cases, and statistically significant high pr expression in both acute and chronic infection cases compared to the control secretory cases (p< 0.05). conclusions: schistosomiasis mansoni seems to have an important impact on the hormone expression of affected women. further studies to explore the mechanism of such changes are recommended.
Extramedullary hematopoiesis in murine schistosomiasis mansoni
Lenzi, H. L.;Lenzi, J. A.;Rosman, F. C.;Pelajo-Machado, M.;Mota, E. M.;Panasco, M. S.;Oliveira, D. N.;
Memórias do Instituto Oswaldo Cruz , 1995, DOI: 10.1590/S0074-02761995000200008
Abstract: during schistosoma mansoni infection, there is morphological evidence of involvement of various hematopoietic growth factors, which cause eosinophil, neutrophil, megakaryocytic and erythroid extramedullary foci in the liver, lymph nodes and omental and mesenteric milky spots. while the eosinophil metaplasia in the periphery of hepatic granulomas roughly reproduced the intensity of the medullary eosinopoiesis, the neutrophil metaplasia, on the contrary, was more intense during the period of neutrophil depression in the bone marrow. this fact suggests that extramedullary hematopoietic foci are locally regulated, and amplify and/or compensate the systemic hematopoietic response during the infection.
High fat diet has a prominent effect upon the course of chronic schistosomiasis mansoni in mice
Alencar, Alba Cristina Miranda de Barros;Neves, Renata Heisler;águila, Márcia Barbosa;Mandarim-de-Lacerda, Carlos Alberto;Gomes, Delir Corrêa;Machado-Silva, José Roberto;
Memórias do Instituto Oswaldo Cruz , 2009, DOI: 10.1590/S0074-02762009000400013
Abstract: this study investigated whether a long-term high-fat diet has an effect on the outcome of chronic murine schistosomiasis mansoni compared to a standard diet. swiss webster female mice (3 weeks old) were fed each diet for up to six months and were then infected with 50 schistosoma mansoni cercariae. their nutritional status was assessed by monitoring total serum cholesterol and body mass. infected mice were examined 6-17 weeks post infection to estimate the number of eggs in faeces. mice were euthanised the next day. total serum cholesterol was lower in infected mice in comparison to uninfected controls (p = 0.0055). in contrast, body mass (p = 0.003), liver volume (p = 0.0405), spleen volume (p = 0.0124), lung volume (p = 0.0033) and faecal (p = 0.0064) and tissue egg density (p = 0.0002) were significantly higher for infected mice fed a high-fat diet. from these findings, it is suggested that a high-fat diet has a prominent effect on the course of chronic schistosomiasis mansoni in mice.
The investigation of protective concomitant immunity in murine schistosomiasis mansoni  [PDF]
Abdel-Moneim M. Salim, Alaa B. Ismael
Open Journal of Immunology (OJI) , 2012, DOI: 10.4236/oji.2012.23016
Abstract: The present study was conducted mainly to establish a new concomitant immunity model to Schistosoma mansoni in mice and assess its effects on the resistance of mice to a challenge infection with a possibility of using as a diagnostic marker. Three groups (A, B and C) of BALB/c mice were infected with a single dose of S. mansoni cercariae obtained from infected Biomphalaria glabrata snail. The group A mice were used as infected control group. The group B mice were intraperitoneally injected with allylthiourea (ATU) 22 days post-primary infection then they were challenged 3 weeks post-ATU treatment. The group C mice were challenged with the same number of cercariae 6 weeks post-primary infection. Perfusion of all mice was done 9 weeks after infection in order to obtain worm burdens. The livers of all mice were obtained for parasitological and pathological assessments. Our results showed that the group B mice had a 29.11% worm reduction rate, 25.37% liver egg reduction rate, and 37.48% granuloma size reduction rate compared to their respective controls. While the group C mice showed superior results and had a 54.66% worm reduction rate, 41.45% liver egg reduction rate, and 51.76% granuloma size reduction rate. It was concluded that these results described novel imaging methods that permit visualization of live schistosomes within their living hosts and may have important implications not only for epidemiological and diagnostic investigations, but also in designing control programs for schistosomiasis including anti-schistosome vaccine.
Cytokine profile associated with human chronic schistosomiasis mansoni
Magalh?es, Andréa;Miranda, Delfin Gonzalez;Miranda, Roberval Gonzalez;Araújo, Maria Ilma;Jesus, Adriana Almeida de;Silva, Angela;Santana, Luciana B;Pearce, Edward;Carvalho, Edgar M;Jesus, Amélia Ribeiro de;
Memórias do Instituto Oswaldo Cruz , 2004, DOI: 10.1590/S0074-02762004000900004
Abstract: this study objective was to evaluate the cytokines associated with early events of hepatic fibrosis in schistosomiasis mansoni. hepatic fibrosis was classified by ultrasonography in 94 patients. immunological evaluation was performed by measurement of secreted cytokines (interleukin il-5, il-10, il-13, interferon-g, tumor necrosis factor-a and transforming growth factors-b) in peripherl blood mononuclear cells stimulated by schistosoma mansoni antigens. significantly, higher levels of il-5, il-10 and il-13 were found in supernatants of sea-stimulated pbmc from subjects with degree iii hepatic fibrosis as compared to patients with degree i or ii fibrosis, significant increases in il-5 and il-13 levels were also observed in some of the subjects who remained untreated for one year following initial assessment and developed more serious fibrosis during this period. the data suggests a role for type 2 cytokines in early stages of hepatic fibrosis in human schistosomiasis mansoni.
Chronic glomerulonephritis associated with hepatosplenic schistosomiasis mansoni
Ramos, Eduardo Antonio Gon?alves;Andrade, Zilton A.;
Revista do Instituto de Medicina Tropical de S?o Paulo , 1987, DOI: 10.1590/S0036-46651987000300008
Abstract: in a series of 36 cases of renal disease associated with hepatosplenic schistosomiasis the following morphologic types of glomerulonephritis were found: mesangio-capillary (33.2%), mesangial proliferative (25.0%), focal glomerular sclerosis (16.7%) and sclerosing glomerulonephritis (8.3%). no significant statistical differences were found when these results were compared with those from 36 cases of glomerulonephritis not associated with hepatosplenic disease. on the other hand, endocapillary glomerulonephritis was found to be predominant in the latter group of cases. these results did not substantiate the assumption that mesangio-capillary glomerulonephritis is specifically related to hepatosplenic schistosomiais. however, if the types of glomerulonephritis that predominantly involve the me-sangium are considered together, they are significantly associated with hepatosplenic schistosomiasis. mesangial involvement is known to occur in other parasitic diseases and that may be related to a common immunopathogenesis.
Egg excretion in the initial phase of experimental murine schistosomiasis mansoni: stability and association with worm burden
Rocha, Regina Lunardi;Rocha, Manoel Otávio da Costa;Pedroso, ênio Roberto Pietra;Colosimo, Enrico Ant?nio;Coelho, Paulo Marcos Zech;
Revista do Instituto de Medicina Tropical de S?o Paulo , 1995, DOI: 10.1590/S0036-46651995000400007
Abstract: stability of faecal egg excretion and correlation with results related to worm burden at the initial phase of schistosomiasis mansoni were observed in two groups of mice infected with different schistosoma mansoni cercarial burdens, by means of analysis of quantitative parasitological studies and schistosome counts after perfusion. thus, it may be stated that few quantitative parasitological stool examinations could be sufficient to express the infection intensity at the initial phase, on the same grounds that it was already demonstrated at the chronic phase. furthermore, it is confirmed that the use of the number of eggs passed in the faeces as a tool to estimate the worm burden at the initial phase of schistosome infection is adequate.
The role of egg antigens, cytokines in granuloma formation in murine schistosomiasis mansoni
Boros, Dov L.;Lukacs, Nicholas W.;
Memórias do Instituto Oswaldo Cruz , 1992, DOI: 10.1590/S0074-02761992000800010
Abstract: the induction of granuloma formation by soluble egg antigens (sea) of schistosoma mansoni is accompanied by t cell-mediated lymphokine production that regulates the intensity of the response. in the present study we have examined the ability of sds-page fractioned sea proteins to elicit granulomas and lymphokine production in infected and egg-immunized mice. at the acute stage of infection sea fractions (<21, 25-30, 32-38, 60-66, 70-90, 93-125, and > 200 kd) that elicited pulmonary granulomas also elicited il-2, il-4 lymphokine production. at the chronic stage a diminished number of fractions (60-66, 70-90, 93-125, and > 200 kd) were able to elicit granulomas with an overall decrease in il-2, il-4 production. granulomas were elicited by larval-egg crossreactive and egg-specific fractions at both the acute and chronic stage of the infection. examination of lymphokine production from egg-immunized mice demonstrated that as early as 4 days il-2 was produced by spleen cells stimulated with <21, 32-38, 40-46, 93-125, and >200 kd fractions. by 16 days, il-2production was envoked by 8 of 9 fractions. il-4 production at 4 days in response to all fractions was minimal while at 16 days il-4 was elicited with the < 21, 25-30, 50-56, 93-125, and > 200 kd fractions. the present study reveals differences in the range of sea fractions able to elicit granulomas and il-2, il-4 production between acute and chronic stages of infection. additionally, this study demonstrates sequential (il-2 followed by il-4) lymphokine production during the primary egg antigen response.
Activity of liver microsomal enzymes during the chronic phase of murine schistosomiasis
Conte, F.P.;Fidalgo-Neto, A.A.;Manh?es-Rocha, D.A.;Paumgartten, F.J.R.;De-Oliveira, A.C.A.X.;
Brazilian Journal of Medical and Biological Research , 2007, DOI: 10.1590/S0100-879X2006005000091
Abstract: the effects of schistosomiasis on microsomal enzymes were studied on post-infection day 90 when accumulated damage and fibrosis are most intense but granulomatous reaction around the eggs harbored in the liver is smaller than during the earlier phases. swiss webster (sw) and dba/2 mice of either sex (n = 12 per sex per group) were infected with 100 schistosoma mansoni cercariae on postnatal day 10 and killed on post-infection day 90. cytochrome p-450 (cyp) concentration and alkoxyresorufin-o-dealkylases (erod, mrod, brod, and prod), p-nitrophenol-hydroxylase (pnph), coumarin-7-hydroxylase (coh), and udp-glucuronosyltransferase (ugt) activities were measured in hepatic microsomes. age-matched mice of the same sex and strain were used as controls. in s. mansoni-infected mice, cyp1a- and 2b-mediated activities (control = 100%) were reduced in sw (erod: male (m) 36%, female (f) 38%; mrod: m 38%, f 39%; brod: m 46%, f 19%; prod: m 50%, f 28%) and dba/2 mice (erod: m 64%, f 58%; mrod: m 60%; brod: f 49%; prod: m 73%) while pnph (cyp2e1) was decreased in sw (m 31%, f 38%) but not in dba/2 mice. coh did not differ between infected and control dba/2 and ugt, a phase-2 enzyme, was not altered by infection. in conclusion, chronic s. mansoni infection reduced total cyp content and all cyp-mediated activities evaluated in sw mice, including those catalyzed by cyp2e1 (pnph), cyp1a (erod, mrod) and 2b (brod, prod). in dba/2 mice, however, cyp2a5- and 2e1-mediated activities remained unchanged while total cyp content and activities mediated by other cyp isoforms were depressed during chronic schistosomiasis.
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