Mansoni-induced Liver Fibrosis Research Articles

Prior Trichinella spiralis infection protects against Schistosoma mansoni induced hepatic fibrosis.

Schistosomiasis affects approximately 250 million people worldwide, with 200,000 deaths annually. It has been documented that the granulomatous response to Schistosoma mansoni (S. mansoni) oviposition is the root cause of progressive liver fibrosis in chronic infection, in 20% of the patients, and can lead to liver cirrhosis and/or liver cancer. The influence of helminths coinfection on schistosomiasis-induced liver pathological alterations remains poorly understood. Therefore, in this study, we investigated the effect of Trichinella spiralis (T. spiralis) infection on S. mansoni-induced hepatic fibrosis. Thirty adult male Balb-c mice were divided into three groups. Group 1 was left uninfected; group 2 was infected with S. mansoni cercariae and group 3 was orally infected with T. spiralis larvae, then 28 days later, this group was infected with S. mansoni cercariae. All groups were sacrificed at the end of the 8th week post infection with S. mansoni to evaluate the effect of pre-infection with T. spiralis on S. mansoni induced liver fibrosis was evaluated parasitologically (worm burden and egg count in tissues), biochemically (levels of alanine aminotransferase and aspartate aminotransferase), histopathologically (H&E and MT staining, and immunohistochemical staining for the expression of α-SMA, IL-6, IL-1β, IL-17, IL-23, TNF-α, and TGF-β). The results in the present study demonstrated marked protective effect of T. spiralis against S. mansoni induced liver pathology. We demonstrated that pre-infection with T. spirais caused marked reduction in the number of S. mansoni adult worms (3.17 ± 0.98 vs. 18 ± 2.16, P = 0.114) and egg count in both the intestine (207.2 ± 64.3 vs. 8,619.43 ± 727.52, P = 0.009) and liver tissues (279 ± 87.2 vs. 7,916.86 ± 771.34; P = 0.014). Consistently, we found significant reductions in both number (3.4 ± 1.1 vs. 11.8.3 ± 1.22; P = 0.007) and size (84 ± 11 vs. 294.3 ± 16.22; P = 0.001) of the hepatic granulomas in mice pre-infected with T. spiralis larvae compared to those infected with only S. mansoni. Furthermore, pre- infection with T. spiralis markedly reduced S. mansoni- induced hepatic fibrosis, as evidenced by decreased collagen deposition, low expression of α-SMA, and significantly reduced levels of IL-17, IL-1B, IL-6, TGF-B, IL-23, and TNF-α compared to mice infected with S. mansoni only. Our data show that pre-infection with T. spiralis effectively protected mice from severe schistosomiasis and liver fibrosis. We believe that our findings support the potential utility of helminths for the preventing and ameliorating severe pathological alterations induced by schistosomiasis.

Resveratrol protects against Schistosoma mansoni-induced liver fibrosis by targeting the Sirt-1/NF-κB axis

Hepatic schistosomiasis is a prevalent form of chronic liver disease that drastically affects human health. Nevertheless, an antifibrotic drug that could suppress the development of hepatic fibrosis does not exist yet. The current study aimed to evaluate the effect of resveratrol, a natural polyphenol with multiple biological activities, on Schistosoma mansoni (S. mansoni)-induced hepatic fibrosis and delineate the underlying molecular mechanism. Swiss male albino mice were randomly assigned into infected and non-infected groups. Hepatic schistosomiasis infection was induced via exposure to S. mansoni cercariae. 6 weeks later, resveratrol was administrated either as 20 mg/kg/day or 100 mg/kg/day for 4 weeks to two infected groups. Another group received vehicle and served as infected control group. At the end of the study, portal hemodynamic, biochemical, and histopathological evaluation of liver tissues were conducted. Remarkably, resveratrol significantly reduced portal pressure, portal and mesenteric flow in a dose-dependent manner. It improved several key features of hepatic injury as evidenced biochemically by a significant reduction of bilirubin and liver enzymes, and histologically by amelioration of the granulomatous and inflammatory reactions. In line, resveratrol reduced the expression of pro-inflammatory markers; TNF-α, IL-1β and MCP-1 mRNA, together with fibrotic markers; collagen-1, TGF-β1 and α-SMA. Moreover, resveratrol restored SIRT1/NF-κB balance in hepatic tissues which is the main switch-off control for all the fibrotic and inflammatory mechanisms. Taken together, it can be inferred that resveratrol possesses a possible anti-fibrotic effect that can halt the progression of hepatic schistosomiasis via targeting SIRT1/ NF-κB signaling.

Anti-fibrotic Effect of Oral Versus Intraperitoneal Administration of Gold Nanoparticles in Hepatic Schistosoma mansoni-Infected Mice.

Schistosomiasis significantly impacts public health, as it causes severe morbidity. Infections caused by Schistosoma mansoni (S. mansoni) can be treated with gold nanoparticles (AuNPs). This study aims to determine the most effective route of AuNPs administration and the magnitude of its anti-fibrotic effect. In the five groups' in vivo assay design, AuNPs were administered intraperitoneally (1mg/kg) and orally (1mg/100g) to S. mansoni-infected mice. Biochemical parameters (serum levels of albumin and liver enzymes alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured. The histological changes of the liver in distinct groups were evaluated using Hematoxylin and Eosin, Masson's trichrome, and immunohistochemical stains. Infection with S. mansoni was associated with substantial changes in the histological architecture of liver tissue and abnormal levels of hepatic function tests (albumin, AST, and ALT). Schistosoma infected hepatocytes exhibited an abnormal microscopic morphology, granuloma formation and aggressive fibrosis. AuNPs restored the liver histological architecture with a highly significant anti-fibrotic effect and significantly corrected hepatic function test levels. Intraperitoneal administration of AuNPs resulted in the most significant anti-fibrotic effect against hepatic S. mansoni infection as observed in all histological sections with Masson's trichrome being the best stain to represent this fact. For treating S. mansoni-induced chronic liver fibrosis, intraperitoneal administration of AuNPs is a successful and effective route of administration that can be recommended.

The potential curative and hepatoprotective effects of platelet rich plasma on liver fibrosis in Schistosoma mansoni experimentally infected mice.

Trapped Schistosoma mansoni eggs trigger fibrotic liver disease that can continue to liver cirrhosis and failure. This work evaluates the outcome of platelet rich plasma (PRP) on S. mansoni-induced liver fibrosis by intraperitoneal (IP) and intrahepatic (IH) routes with/without Praziquantel (PZQ) treatment. Swiss albino mice (n = 162) were divided into non-infected (n = 66) and infected (n = 96) groups, then subdivided into non-treated and treated subgroups with PRP(IP), PRP(IH) 6th and 10th weeks post-infection, PZQ, PZQ + PRP(IP) and PZQ + PRP(IH) 6th and 10th weeks post-infection. Effects of treatments were evaluated by parasitological, histopathological and Immunohistochemical assessments. In the early assessment (12th week post-infection) of infected-treated groups, the mean granuloma number showed significant reduction in groups treated with PZQ + PRP (IH) 10th week, PRP (IP), PZQ + PRP (IP) and PZQ + PRP (IH) 6th week (33.33%, 33%, 27.77% and 27.22%, respectively). Furthermore, the mean granuloma diameter showed significant reduction in groups treated with PRP (IH) 10th week and PZQ + PRP (IP) (24.17% and 15.5%, respectively). Also, the fibrotic index showed significant reduction in groups treated with PZQ + PRP (IP), PRP (IP) and PZQ + PRP (IH) 6th week (48.18%, 46.81% and 41.36%, respectively). Transforming growth factor β1(TGF-β1) expression was in correlation with parasitological and histopathological results. Diminished TGF-β1 expression was mostly in infected groups treated with PZQ + PRP (IP), PZQ + PRP (IH) 6th week and PRP (IP) (88.63%, 88.63% and 77.27%, respectively). In the late assessment (14th week post-infection) of infected treated groups, TGF-β1expression was reduced in groups treated with PZQ, PRP (IH) 10th weeks, PRP (IP) (83.33%, 66.66%, 33.33% respectively). PRP showed promising anti-fibrotic effects on S. mansoni-induced liver fibrosis.

Antifibrotic and anthelminthic effect of casticin on Schistosoma mansoni-infected BALB/c mice.

Schistosomiasis is an important tropical disease caused by Schistosoma. Although the pathogenesis of liver fibrosis has been intensively studied, the choice of effective treatment is still inadequate. In this study, we aimed to investigate the potential of using Casticin to treat Schistosoma mansoni-induced liver fibrosis. BALB/c mice were divided into three groups - control, infection, and treatment group. The infection and treatment group were percutaneously infected with 100-120 cercariae. Mice from the treatment group were treated with 20mg/kg/day Casticin for 14 consecutive days to investigate the potential protective effects of Casticin. Mice were sacrificed and were used for histological, RNA, protein, and parasite burden analysis. Our results showed that hepatic fibrosis was significantly attenuated, as indicated by histology and reduction of fibrotic markers such as collagen AI, transforming growth factor β (TGF-β), and α-smooth muscle actin (α-SMA). Furthermore, Casticin treatment significantly reduced worm burden. Anthelmintic effect of Casticin was also observed by scanning electron microscopy. Collectively, our study suggested that Casticin may be a beneficial candidate in treating S. mansoni infection.

Human Platelet Rich Plasma Alleviates Liver Fibrosis in Murine Schistosomiasis Mansoni

AbstractBackground: Schistosoma (S.) mansoni infection leads to hepatic fibrosis that may cause severe complications. Currently, there is no effective medication against schisto-somiasis liver fibrosis.Aim of the Work: The aim of the present study was to evaluate the anti-fibrotic effects of human platelet rich plasma (PRP) against S. mansoni liver fibrosis in experimentally infected mice alone or in combination with praziquantel (PZQ).Materials and Methods: Seventy male BALB/c mice were divided into five mice groups; group I: Uninfected control (UC, n=10); group II: Infected, untreated (IU, n=15); group III: infected, treated 8 weeks post-infection (p.i.) with PZQ (PZQ, n=15); group IV: Infected, received 8 weeks p.i. PRP (PRP, n=15) and group V: Infected, treated 8 weeks p.i. with PZQ then received PRP (PZQ+PRP, n=15). All the mice were euthanized at 12 weeks p.i then parasitological, histopatholog-ical, immunohistochemical studies were done in addition to measuring of serum liver enzymes.Results: PZQ+PRP significantly reduced (p<0.001) the mean liver granuloma diameter by 71%, followed by PRP (51.2%) and then PZQ (33.8%). Also, PZQ+PRP achieved the highest reduction in the liver fibrosis (73.3%), whereas PRP achieved 63.8% reduction in the fibrosis and this was better than that revealed by PZQ (50.8%). On immunohisto-chemical examination of the liver sections, PZQ+PRP caused the least expression of alpha smooth muscle actin (a-SMA), transforming growth factor-b1 (TGF-b1) and inducible nitric oxide synthase (iNOS), while it induced the strongest caspase-3 expression, among the treated mice groups, in comparison to IU mice. PRP alone or in combination with PZQ significantly decreased serum liver enzymes comparing to IU mice.Conclusion: PZQ+PRP significantly reduced S. mansoni induced liver fibrosis in association with improving the liver enzymes. So, it is recommended to treat S. mansoni liver fibrosis by both PZQ and PRP, and this could be applicable in case of human liver fibrosis caused by schistosomiasis mansoni.

Ziziphus spina-christi leaf extract ameliorates schistosomiasis liver granuloma, fibrosis, and oxidative stress through downregulation of fibrinogenic signaling in mice.

Schistosomiasis is a widespread parasitic infection that affects humans, as well as wild and domestic animals. It ranks second after malaria, with a significant health and socio-economic impact in the developing countries. The objective of this study was to assess the anti-schistosomal impact of Ziziphus spina-christi leaf extract (ZLE) on Schistosoma mansoni-induced liver fibrosis in CD-1 Swiss male albino mice. S. mansoni infection was achieved by dipping of mouse tails in schistosomal cercariae. ZLE treatment was initiated at 46 days post-infection by administering a dose of the extract on a daily basis for 10 consecutive days. S. mansoni infection resulted in liver granuloma and fibrosis, with a drastic elevation in liver function factors, nitric oxide, and lipid peroxidation, which were associated with a reduction in glutathione content and substantial inhibition of antioxidant enzyme activities compared to those of the control. Induction of hepatic granuloma, oxidative stress, and fibrosis in the liver was controlled by ZLE administration, which also produced inhibition of matrix metalloproteinase-9, alpha-smooth muscle actin, transforming growth factor-β, and tissue inhibitors of metalloproteinases expressions. In addition, the S. mansoni-infected group exhibited an increase in Bax and caspase-3 levels and a decrease in Bcl-2 level. However, treatment with ZLE mainly mitigated apoptosis in the liver. Thus, the findings of this study revealed that Ziziphus spina-christi had anti-apoptotic, anti-fibrotic, antioxidant, and protective effects on S. mansoni-induced liver wounds. The benefits of Ziziphus spina-christi extract on S. mansoni were partly partially mediated by enhancing anti-fibrinogenic and nuclear factor erythroid 2–related factor 2 (Nrf2) pathways.

Corrigendum: Wharton's jelly-derived mesenchymal stem cells combined with praziquantel as a potential therapy for Schistosoma mansoni-induced liver fibrosis.

Scientific Reports 6: Article number: 21005; published online: 15 February 2016; updated: 02 September 2016 In this Article, Affiliation 4 is incomplete. The correct affiliation is listed below: Department of Virology and Immunology, Cancer Biology Department, National Cancer Institute, Cairo University, Children’s Cancer Hospital Egypt 57357, Cairo 11712, Egypt.

Sodium valproate, a histone deacetylase inhibitor, with praziquantel ameliorates Schistosoma mansoni-induced liver fibrosis in mice

AimsThis study explores the potential antifibrotic effect of sodium valproate (SV), an inhibitor of class I histone deacetylase (HDAC) enzymes, and/or praziquantel (PZQ) on Schistosoma mansoni (S. mansoni)-induced liver fibrosis in mice. Main methodsMale Swiss albino mice were divided into nine groups: group I- normal control (NC); group II- uninfected gum mucilage (GM) treated; group III- uninfected PZQ- treated; group IV- uninfected SV-treated; group V- control S. mansoni infected mice; group VI- infected GM-treated; group VII- infected PZQ-treated; group VIII- infected SV-treated; group IX- infected PZQ+SV treated. All SV administrations were 300mg/kg/day orally and administered for five weeks beginning on the 5th week post infection (WPI). All PZQ administrations were 500mg/kg/day orally and administered for 2 consecutive days beginning on the 7th WPI. Serum transforming growth factor-beta 1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), hepatic hydroxyproline (Hyp) content, and liver function tests (AST and ALT) were determined. Specimens of the hepatic tissues were examined histologically. Key findingsTreatment of S. mansoni-infected mice with SV significantly decreased the serum levels of ALT, TGF-β1 and TNF-α, and the liver tissue hydroxyproline content compared with the S. mansoni infected untreated groups. Histologically, treatment with SV revealed regression of the granulomatous inflammatory reaction. Combined treatment with PZQ and SV produces more favorable biochemical results, and aborted granulomatous reaction compared with either drug alone. SignificanceSodium valproate is a promising anti-fibrotic agent. It demonstrated an anti-fibrotic effect in early stages of S. mansoni infection through downregulation of profibrogenic cytokines, and collagen deposition.

Wharton's jelly-derived mesenchymal stem cells combined with praziquantel as a potential therapy for Schistosoma mansoni-induced liver fibrosis.

Liver fibrosis is one of the most serious consequences of S. mansoni infection. The aim of the present study was to investigate the potential anti-fibrotic effect of human Wharton’s jelly-derived mesenchymal stem cells (WJMSCs) combined with praziquantel (PZQ) in S. mansoni-infected mice. S. mansoni-infected mice received early (8th week post infection) and late (16th week post infection) treatment with WJMSCs, alone and combined with oral PZQ. At the 10th month post infection, livers were collected for subsequent flow cytometric, histopathological, morphometric, immunohistochemical, gene expression, and gelatin zymographic studies. After transplantation, WJMSCs differentiated into functioning liver-like cells as evidenced by their ability to express human hepatocyte-specific markers. Regression of S. mansoni-induced liver fibrosis was also observed in transplanted groups, as evidenced by histopathological, morphometric, and gelatin zymographic results besides decreased expression of three essential contributors to liver fibrosis in this particular model; alpha smooth muscle actin, collagen-I, and interleukin-13. PZQ additionally enhanced the beneficial effects observed in WJMSCs-treated groups. Our results suggest that combining WJMSCs to PZQ caused better enhancement in S. mansoni-induced liver fibrosis, compared to using each alone.

P0024 : Efficacy of wharton’s jelly-derived mesenchymal stem cells combined with praziquantel in schistosoma mansoni-induced liver fibrosis in mice

P0024 : Efficacy of wharton’s jelly-derived mesenchymal stem cells combined with praziquantel in schistosoma mansoni-induced liver fibrosis in mice

Biochemical and Parasitological Studies on the Effect of hUCB-Selected CD34(+) Progenitor/Stem Cells in Mice Infected with Schistosoma mansoni.

Background and Objectives:Placenta and blood that remained in the umbilical cord is routinely available as a discarded tissue after deliveries and it is free of any legal, moral, ethical or religious objections, providing a high number of multipotent CD34+ progenitor and stem cells. Using ex vivo isolated CD34+ cells from human umbilical cord blood (hUCB) have emerged as promising candidates to treat various diseases, including exogenous pathogenic infections. We have expanded to build a rational approach to study the effect of CD34+ cells after damaged liver tissues by the devastating human parasitic flatworm Schistosoma mansoni.Methods and Results:Experimental studies were conducted in the Department of Zoology, Faculty of Science and Departments of Parasitology and Physiology, Faculty of Medicine, SCU, Egypt. We have studied the impact of ex vivo preparation of CD34+ cells from hUCB on S. mansoni-induced liver fibrosis de novo, and treated for shorter and longer periods in vivo. Ova count, ALT and albumin were measured at specific time interval and histopathological examination of liver was conducted to confirm the biochemical results. The data obtained were statistically analyzed by ANOVA between groups. It was found that the administration of CD34+ cells have modestly reduced liver damage; reduced the S. mansoni infection associated elevation in serum levels of ALT; significantly improved serum levels of albumin and reduced egg granuloma diameter in the livers.Conclusions:We demonstrated that CD34+ cells can markedly ameliorated liver fibrosis in vivo and may be beneficial for therapy to recover organ structure and/or function of S. mansoni-infected mice.

Telmisartan, an AT1 receptor blocker and a PPAR gamma activator, alleviates liver fibrosis induced experimentally by Schistosoma mansoni infection

BackgroundHepatic schistosomiasis is considered to be one of the most prevalent forms of chronic liver disease in the world due to its complication of liver fibrosis. The demonstration of the pro-fibrogenic role of angiotensin (Ang) II in chronic liver disease brought up the idea that anti-Ang II agents may be effective in improving hepatic fibrosis by either blocking Ang II type 1 (AT1) receptors or inhibiting the angiotensin converting enzyme. Peroxisome proliferator-activated receptors gamma (PPARγ) activation has been also shown to inhibit hepatic stellate cell activation and progression of fibrosis. The present study has aimed at testing the anti-fibrogenic effects of telmisartan; an AT1 receptor blocker and a PPARγ partial agonist, alone or combined with praziquantel (PZQ) on Schistosoma mansoni-induced liver fibrosis in mice.MethodsTo achieve the aim of the study, two sets of experiments were performed in which telmisartan was initiated at the 5th (set 1) and the 10th (set 2) weeks post infection to assess drug efficacy in both acute and chronic stages of liver fibrosis, respectively. Schistosoma mansoni-infected mice were randomly divided into the following four groups: infected-control (I), telmisartan-treated (II), PZQ-treated (III), and telmisartan+PZQ-treated (IV). In addition, a normal non-infected group was used for comparison. Parasitological (hepatomesenteric worm load and oogram pattern), histopathological, morphometric, immunohistochemical (hepatic expressions of matrix metalloproteinase-2; MMP-2 and tissue inhibitor of metalloproteinase-2; TIMP-2), and biochemical (serum transforming growth factor beta 1; TGF-β1 and liver function tests) studies were performed.ResultsTelmisartan failed to improve the parasitological parameters, while it significantly (P<0.05) decreased the mean granuloma diameter, area of fibrosis, and serum TGF-β1. Additionally, telmisartan increased MMP-2 and decreased TIMP-2 hepatic expression. Combined treatment failed to show any additive properties, yet it did not affect the anti-schistosomal activity of PZQ.ConclusionsThese results suggest potential anti-fibrotic effects of telmisartan, an AT1 receptor blocker and a PPARγ partial agonist, in acute and chronic stages of Schistosoma mansoni–induced liver fibrosis in mice.

Amelioration of Murine Schistosoma mansoni Induced Liver Fibrosis by Mesenchymal Stem Cells

Schistosomiasis is a common chronic helminthic infection of the liver that causes hepatic fibrosis and portal hypertension,contributing to the death of over half a million people a year. Infusion of autologous bone marrow cells into patients with hepatic cirrhosis has been reported to ameliorate symptoms of portal hypertension and improve liver function, either by conversion of the infused mesenchymal stem cells (MSCs) to hepatocytes or by modulating of the hepatic fibrosis. Here,we have investigated the antifibrotic effect of mesenchymal stem cells (MSCs) using S. mansoni-induced liver fibrosis in mice, which causes an intense, stable fibrosis. MSCs derived from bone marrow of male mice were then infused intravenously into female mice that had received intraperitoneal injection of S.mansoni cercariae. Mice were divided into 4 groups: Untreated control; MSCs infusion only; Schistosomiasis only; and Schistosomiasis plus MSCs infusion. Serum alanine aminotransferase (ALT) and liver histopathology were evaluated. Expression of the collagen gene (type I),transforming growth factor (TGF-β), matrix metalloproteinase (MMP2), tissue inhibitor of metalloproteinase (TIMP-1),stromal cell-derived factor-1(SDF-1) and its receptor (CXCR4) were analyzed. MSC infusion resulted in significant decrease in liver collagen and TGF-β gene expression in the Schistosomiasis mice. The ratio of MMP-2 to TIMP-1 expression increased. SDF-1 and CXCR4 mRNA expression also increased. There was overall improvement of liver histology and a statistically significant reduction of serum ALT level. MSCs infusion ameliorated S. mansoni-induced liver fibrosis, probably by modulating the relative expression of MMP and TIMP. The findings support the hypothesis that MSCs participate in liver regeneration and functional improvement by reducing liver fibrosis.

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

BackgroundPraziquantel (PZQ) is an isoquinoline derivative (2-cyclohexylcarbonyl-1, 2, 3, 6, 7, 11b-hexahydro-4H-pyrazino{2,1-a}-isoquinoline-4-one), and is currently the drug of choice for all forms of schistosomiasis. Silymarin, a standardized milk thistle extract, of which silibinin is the main component, is known for its hepatoprotective, anti-inflammatory, antioxidant activities, and hepatocyte regeneration. This study investigates the anti-inflammatory/anti-fibrotic effects of silymarin and/or PZQ on schistosomal hepatic fibrosis.MethodsSchistosoma mansoni-infected mice were divided into two large groups (I & II), each with four subgroups and were run in parallel. (i) Infected untreated; (ii) treated with silymarin, starting from the 4th (3 weeks before PZQ therapy) or 12th (5 weeks after PZQ therapy) weeks post infection (PI); (iii) treated with PZQ in the 7th week PI; and (iv) treated with silymarin, as group (ii) plus PZQ as group (iii). Comparable groups of uninfected mice run in parallel with the infected groups. Mice of groups I and II were killed 10 and 18 weeks PI, respectively. Hepatic content of hydroxyproline (HYP), serum levels and tissue expression of matrix metalloproteinase-2 (MMP-2), transforming growth factor-β1 (TGF-β1) and number of mast cells were determined. In addition, parasitological, biochemical and histological parameters that reflect disease severity and morbidity were examined.ResultsSilymarin caused a partial decrease in worm burden; hepatic tissue egg load, with an increase in percentage of dead eggs; modulation of granuloma size, with significant reduction of hepatic HYP content; tissue expression of MMP-2, TGF-β1; number of mast cells, with conservation of hepatic reduced glutathione (GSH). PZQ produced complete eradication of worms, eggs and alleviated liver inflammation and fibrosis. The best results were obtained, in most parameters studied, in groups of mice treated with silymarin in addition to PZQ.ConclusionsOur results point to silymarin as a promising anti-inflammatory and anti-fibrotic agent; it could be introduced as a therapeutic tool with PZQ in the treatment of schistosomal liver fibrosis, but further studies on mechanisms of silymarin and PZQ in chronic liver diseases may shed light on developing therapeutic methods in clinical practice.

Prevention and treatment of Schistosoma mansoni-induced liver fibrosis in mice

The present study was designed to examine the potential preventive and curative effects of curcumin, resveratrol, imatinib, rosiglitazone, losartan and bosentan (BOS) on Schistosoma mansoni-induced liver fibrosis in mice. Induction of liver fibrosis was produced in male Swiss mice by subcutaneous injection of S. mansoni cercariae per mouse. Mice were left for 28 days before starting the experiment then mice were divided into two main groups. The first group was further subdivided into experimental groups and started drug treatment at day 28 after infection and continued for 2 weeks in order to evaluate the potential preventive effects of the mentioned drugs on S. mansoni-induced liver fibrosis. The second group of mice were left for 2 weeks and then treated with praziquantel for two consecutive days to eradicate the worms and so stop egg disposition and further fibrosis development. Mice were then subdivided into the experimental groups and drug treatment was started for 2 weeks to evaluate their efficacy to decrease the developed fibrosis. At the end of the experiment period, mice were killed and serum was collected for the estimation of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin and albumin. Liver tissue was taken for the estimation of hepatic hydroxyproline content and histopathological examination to confirm the biochemical results. Results of the study indicate that curcumin and imatinib have potent antifibrotic activity both in suppressing and reversing S. mansoni-induced liver fibrosis, while resveratrol has beneficial effects only in suppressing the development of S. mansoni-induced liver fibrosis.