Anti-inflammatory/anti-fibrotic effects of the hepatoprotective silymarin and the schistosomicide praziquantel against Schistosoma mansoni-induced liver fibrosis

Preschool children suffer from morbidity attributable to Schistosoma mansoni. We compared a single and double dose of praziquantel treatment on the regression of S. mansoni associated morbidity in children less than six years in Uganda. We measured the sizes of spleen and liver as well as liver fibrosis before treatment and 8 months after treatment among children who either received one dose (n = 201) or two doses (n = 184) of praziquantel (standard oral dose of 40 mg/kg body weight). Heamoglobin measurements were also taken. Overall, liver enlargement reduced from 52.2% (95% CI (Confidence interval) 45.1, 59.3) to 17.9% (95% CI 12.9, 23.9) with a single dose and from 48.4 (95% CI 40.9, 55.8) to 17.9% (95% CI 12.7, 24.3) with a double dose and there was no significant difference between the changes in proportion of children with enlarged liver between the two treatment groups. The proportion of children with enlarged spleen was not significantly reduced in the group treated with either one or two doses, 47.8% (95% CI 41.7, 54.9) to 45.3% (95% CI 38.3, 52.4) and 48.4% (95% CI 40.9,55.8) to 40.8% 95% CI 33.6, 48.2), respectively. Liver fibrosis detected among children getting single dose (n = 9) or double doses (n = 13) resolved after treatment with praziquantel. The number of children with low heamoglobin significantly reduced from 51.2% (95% CI 44.1, 58.3) to 0.5% (0.2, 0.8) and 61.4% (95% CI 53.9,68.5) to 1.1% (95% CI 0.1, 3.9) after single and double dose treatment, respectively. These results suggest that there is no evidence of a difference in effect between one dose of praziquantel and two doses in reversing morbidity attributable to S. mansoni among children less than six years of age.

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Plasma levels of innate immune mediators are associated with liver fibrosis in low parasite burden Schistosoma mansoni- infected individuals

Scandinavian Journal of Immunology ◽

10.1111/sji.12642 ◽

2018 ◽

Vol 87 (3) ◽

pp. e12642 ◽

Cited By ~ 4

Author(s):

J. L. Rodrigues Oliveira ◽

M. M. Teixeira ◽

J. R. Lambertucci ◽

C. M. F. Antunes ◽

M. Carneiro ◽

...

Keyword(s):

Liver Fibrosis ◽

Schistosoma Mansoni ◽

Plasma Levels ◽

Parasite Burden ◽

Innate Immune ◽

Immune Mediators

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The anti-inflammatory and anti-fibrotic effects of tadalafil in thioacetamide-induced liver fibrosis in rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2018-0338 ◽

2018 ◽

Vol 96 (12) ◽

pp. 1308-1317 ◽

Cited By ~ 9

Author(s):

Heba M. Mansour ◽

Abeer A.A. Salama ◽

Rania M. Abdel-Salam ◽

Naglaa A. Ahmed ◽

Noha N. Yassen ◽

...

Keyword(s):

Liver Fibrosis ◽

Inflammatory Cytokines ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Smooth Muscle Actin ◽

Interleukin 1 ◽

Health Concern ◽

Dependent Manner ◽

Serum Transaminases ◽

Anti Inflammatory

Liver fibrosis is a health concern that leads to organ failure mediated via production of inflammatory cytokines and fibrotic biomarkers. This study aimed to explore the protective effect of tadalafil, a phosphodiesterase-5 inhibitor, against thioacetamide (TAA)-induced liver fibrosis. Fibrosis was induced by administration of TAA (200 mg/kg, i.p.) twice weekly for 6 weeks. Serum transaminases activities, liver inflammatory cytokines, fibrotic biomarkers, and liver histopathology were assessed. TAA induced marked histopathological changes in liver tissues coupled with elevations in serum transaminases activities. Furthermore, hepatic content of nitric oxide and tumor necrosis factor-alpha, interleukin-6, and interleukin-1 beta were elevated, together with a reduction of interleukin-10 in the liver. In addition, TAA increased hepatic contents of transforming growth factor-beta, hydroxyproline, alpha-smooth muscle actin, and gene expression of collagen-1. Pretreatment with tadalafil protected against TAA-induced liver fibrosis, in a dose-dependent manner, as proved by the alleviation of inflammatory and fibrotic biomarkers. The effects of tadalafil were comparable with that of silymarin, a natural antioxidant, and could be assigned to its anti-inflammatory and anti-fibrotic properties.

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Complementary effect of Capparis spinosa L. and silymarin with/without praziquantel on mice experimentally infected with Schistosoma mansoni

Helminthologia ◽

10.1515/helm-2017-0055 ◽

2018 ◽

Vol 55 (1) ◽

pp. 21-32

Author(s):

S. S. El-Hawary ◽

K. F. Taha ◽

F. N. Kirillos ◽

A. A. Dahab ◽

A. A. El-Mahis ◽

...

Keyword(s):

Liver Fibrosis ◽

Schistosoma Mansoni ◽

Hepatic Fibrosis ◽

Colorimetric Assay ◽

Quantitative Estimation ◽

Scar Tissue ◽

Egg Load ◽

Total Polyphenols ◽

Capparis Spinosa ◽

Serum Aminotransferases

SummarySchistosomiasis remains to be the most common fibrotic disease resulting from inflammation and deposition of scar tissue around trapped parasitic eggs in the liver. Though chemotherapy eradicates matured worms efficiently and prevents the accumulation ofschistosomeeggs, fewer effective drugs are directed to reverse the present hepatic fibrosis. Therefore, treatment targeting hepatic fibrosis associated with schistosomiasis remains a challenging proposition.The present study was designed to investigate the potential complementary schistosomicidal and hepatoprotective activities of the methanol extract ofCapparis spinosaL. (C. spinosa) with or without praziquantel (PZQ) and compare results with silymarin (Milk thistle), a known hepatoprotective and antifibrotic agent, on induced liver fibrosis by experimentalSchistosoma mansoni(S. mansoni) infection. Total polyphenols in the extract were determined using colorimetric assay.C. spinosaL. caused a partial decrease in worm burden; a statistically significant reduction in hepatic and intestinal tissue egg load, what was associated histopathologically with decreasing in both the number and diameter of granulomas, as well as restoring serum aminotransferases (AST & ALT), alkaline phosphatase (ALP) and improving liver albumin synthesis. The best results were obtained in the group of mice treated withC. spinosaL. and PZQ together. Quantitative estimation of total polyphenols content using colorimetric assay showed thatC. spinosaL. leaves contain higher concentration of polyphenolic compounds than fruits.It was concluded thatC. spinosaL. has a promising hepatoprotective and antifibrotic properties and could be introduced as a safe and effective therapeutic tool with PZQ in the treatment of schistosomal liver fibrosis. Nevertheless further studies on the mechanism of action ofC. spinosaL. in chronic liver diseases may shed light on developing therapeutic methods in clinical practice.

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