Vitamin E reduces hepatic fibrosis in mice with Schistosoma japonicum infection.

To investigate whether vitamin E protects against hepatic fibrosis in mice with Schistosoma japonicum infection, 24 pathogen-free Kunming mice were selected and randomly divided into four groups: control (uninfected, untreated), model (infected, untreated), low-dose intervention (infected, vitamin E-treated, 30 mg/g bodyweight/day) and high-dose intervention (infected, vitamin E-treated, 60 mg/g bodyweight/day). Mice were infected with Schistosoma japonicum by inoculating abdominal skin with snail hosts. The activities of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were detected in hepatic tissue by colorimetry. The expression levels of laminin (LN), hyaluronic acid (HA), procollagen type Ⅲ (PC-III) and type Ⅳ collagen (IV-C) were detected in the serum by radioimmunoassay. Finally, areas and numbers of granulomas were assessed through histopathology 42 days following treatment. The results revealed that mean areas of granulomas were smaller in the low- and high-dose intervention groups compared to those in the model group. Furthermore, the higher dose of vitamin E resulted in smaller granulomas than the low dose. The levels of LN, HA, PC-III and IV-C in the serum were lower following vitamin E treatment than in the model group. By contrast, activity of SOD, GPx and CAT in hepatic tissue was higher following vitamin E treatment compared to the model group. The activity of MDA was lower in hepatic tissue following vitamin E treatment compared to the model group, but was higher compared to controls. In general, the higher dose of vitamin E affected measurements to a greater extent than the lower dose. In conclusion, vitamin E treatment may reduce the growth of granulomas, slowing the process of hepatic fibrosis, and this effect may be the result of the altered activity of the oxidation-reduction enzyme system.

[Inhibitory effect of total flavonoids of Malus hupehensis on hepatic fibrosis induced by Schistosoma japonicum in mice].

OBJECTIVE: To investigate the effects of total flavonoids of Malus hupehensis on hepatic fibrosis in mice induced by Schistosoma japonicum. METHODS: The mice model of hepatic fibrosis which infected by cercariae of S. japonicum were randomly divided into 6 groups: Group A as a blank control, Group B as a model, Group C as a positive control by complex liver soften tablet of turtle, Group D, E, F treated with a high dose of 114 mg/(kg x d), middle dose of 57 mg/(kg d), and low dose of 28.5 mg/(kg x d) of total flavonoids of Malus hupehensis, respectively. Every group had 10 mice. Each group of C, D, E, F was orally given praziquantel at a dose of 500 mg/(kg x d) for 2 d, on 42 d after the infection, and then administered with total flavonoids of Malus hupehensis for 60 d. Group A and B were orally given with sodium chloride. All the mice were killed at the end of the administration. Serum hyaluronic acid (HA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected; hydroxyproline in liver tissues was detected; areas of egg granuloma and degrees of hepatic fibrosis were observed via HE and Masson staining. RESULTS: Compared with the blank control Group A, the egg granuloma appeared obviously, the collagen deposit and fibrosis occurred in liver tissues of Group B, C, D, E, F. The levels of ALT, AST, HA in sera and HYP in liver tissues were significantly higher (P < 0.05 or P < 0.01). However, the levels of ALT, AST, HA and HYP in the high, middle and low dose groups of total flavonoids were significantly lower than those in the model Group B (P < 0.05 or P < 0.01), the areas of egg granuloma, the collagen deposits and the degrees of hepatic fibrosis in Group C, D, E, F were significantly lower than those in the model Group B. CONCLUSION: The total flavonoids of Malus hupehensis have an obviously inhibitory effect on the hepatic fibrosis induced by Schistosomajaponicum infection.

Paeoniflorin ameliorates schistosomiasis liver fibrosis through regulating IL-13 and its signalling molecules in mice.

Treatment of liver fibrosis associated with Schistosoma japonicum ova-induced granulomas remains a challenging proposition. Paeoniflorin (PAE, C23H28O11) has anti-inflammatory, anti-allergic, and immunoregulatory effects and it is commonly used in Chinese Herbal prescriptions to treat hepatic disorders. The present study was carried out to investigate the effects of PAE on hepatic fibrosis of mice infected with S. japonicum and to explore its possible mechanism. Upon pathological examination of PAE-treated mice, the size of egg granuloma, fibrosis scores, the concentration of IL-13 and hydroxyproline in liver were significantly reduced compared with the model mice. In the primary culture of hepatic stellate cells (HSCs), PAE inhibited IL-13-induced collagen synthesis. These results suggested that PAE might alleviate the hepatic granulomas and fibrosis caused by S. japonicum and the inhibitory effect of PAE on hepatic fibrosis might be associated with its ability to decrease the level of IL-13 and to interfere with the IL-13 signalling molecule in HSCs.

[Therapeutic effect of Haobieyangyinruanjianfang on the mouse liver fibrosis caused by schistosomiasis].

OBJECTIVE: To explore therapeutic effect of Haobieyangyinruanjianfang (HBYYRJ) on mouse liver fibrosis by schistosomiasis. METHODS: Mice except for normal control were infected with Japanese schistosome cercarias, after 12 weeks, infected mice were divided into 7 groups: low HBYYRJ group, middle HBYYRJ group, high HBYYRJ group, Fufangbiejiaruangan tablet (FFBJRG) group, colchicine group, 3 months infection group and 6 months infection group. Hepatic fibrosis was found in 3 months infection group. Liver hydroxyproline (Hyp) was determined, matrix metalloproteinase-2 and 9 (MMP-2, MMP-9) were detected with gelatin zymography, serum hyaluronic acid (HA) and precollagen III (PC-III) were detected using RIA. RESULTS: HBYYRJ obviously reduced hepatic fibrosis (probability value less than 0.01). Collagen and HA in 3 months infection group and 6 months infection group were higher than that in normal group (probability value less than 0.01), collagen in high and middle HBYYRJ groups and HA in middle and low HBYYRJ groups were lower than that in 6 months infection group (P less than 0.01, probability value less than 0.05). The expression of MMP-9 and MMP-2 in 3 months infection group and 6 months infection group was higher than that in normal group (probability value less than 0.01), The expression of MMP-9 in three HBYYRJ groups and the expression of MMP-2 in high HBYYRJ group were lower than that in 6 months infection group (probability value less than 0.05). CONCLUSION: HBYYRJ can reduce liver fibrosis caused by schistosomiasis.

Effect of anluohuaxian tablet combined with gamma-IFN on schistosomal liver fibrosis.

The therapeutic effects of anluohuaxian tablet combined with gamma-IFN on schistosomal liver fibrosis and its mechanism were studied in a murine model and clinical cases of schistosomal liver fibrosis. Fifty Kunming mice were randomly divided into 5 groups: normal control group, infection control group, anluohuaxian tablet-treated group, gamma-IFN-treated group and combined treatment (anluohuaian tablet+gamma-IFN) group. Pathologic changes in liver, including hepatic pigmentation and the size of schistosomal egg granuloma, were observed by HE staining after treatment for 8 weeks. The expression of the type I and collagen III, and TIMP-1 was detected by immunohistochemistry. TGF-beta1 mRNA expression was examined by real-time fluorescent quantitative PCR. Sixty patients with schistosomal liver fibrosis were divided into treatment group and control group. The patients in treatment group were treated with anluohuaxian tablet in combination with gamma-IFN for 6 months. Before and after treatment, the changes of symptoms and signs, liver function, serum liver fibrosis indexes and imaging indexes were observed. The results showed that as compared with infection control group, all forms of treatments relieved the hepatic pathological injury with apparently diminished size of schistosomal egg nodules and decreased percentage of pigmentation (P<0.05). Furthermore, the expression of collagen I and III, TIMP-1, and TGF-beta1 mRNA in combined treatment group was significantly decreased as compared with anluohuaxian tablet-treated and gamma-IFN-treated groups (P<0.05). In the clinical observation, the serum liver fibrosis indexes, the portal vein width as well as the spleen thickness was significantly reduced in treatment group as compared with control group (P<0.05). It was concluded that the combined use of anluohuaxian tablet with gamma-IFN in schistosomal liver fibrosis could protect liver function, alleviate liver fibrosis, and could be used as a choice in treating patients with schiatosomal liver fibrosis.

Paeoniflorin: a monomer from traditional Chinese medical herb ameliorates Schistosoma japonicum egg-induced hepatic fibrosis in mice.

Treatment of liver fibrosis associated with Schistosoma japonicum ova-induced granulomas remains a challenging proposition. There is a close relationship between high levels of interleukin-13 (IL-13) and the development of severe schistosome fibrosis. In contrast, IL-13 receptor (R) α2 has an effective role in attenuation of profibrosis. Several Chinese herbs have significant beneficial effects in liver disease. Accordingly, the purpose of the present study was to investigate the therapeutic effect of Paeoniflorin (PAE) on liver fibrosis. A mouse model for liver fibrosis was established, using infection with S. japonicum cercariae via the skin. Liver tissue was used to examine the effect of PAE on hydroxyproline, collagen I and III, and IL-13 and IL-13Rα2. The results showed that PAE has significant suppressive effect on the increase of both hepatic hydroxyproline and collagen I and III, which are the main components of extracellular matrix (ECM). Meanwhile, PAE not only inhibits IL-13 production, it also elevates IL-13Rα2 in PAE-pretreated groups compared with controls. These results suggested that PAE can improve liver fibrosis due to S. japonicum infection. The effect of PAE appears to depend on a decrease of IL-13 and an increase of IL-13Rα2.

[Study on the effect of heluoshugan capsule on liver fibrosis induced by Schistosoma japonicum infection in mice].

OBJECTIVE: To investigate the effect of Chinese traditional medicine heluoshugan capsule on liver fibrosis induced by Schistosoma japonicum infection in mice. METHODS: Liver fibrosis in mice was established by Schistosoma japonicum infection in 6 weeks. Suspension of heluoshugan prepared with normal saline was given orally to the mice, 2 capsules for 20 mice daily for 8 weeks. The level of vascular endothelial growth factor (VEGF), focal adhesion kinase (FAK) and type I, III collagen in liver tissue were detected by immuno-histochemistry. RESULTS: The results showed that heluoshugan improved the pathological change of the liver tissue, decreased the level of type I, III collagen, especially type III collagen (P < 0.01). The level of VEGF and FAK expression was inhibited after the administration of heluoshugan, though the level usually increased in liver fibrosis due to the infection. CONCLUSIONS: The result suggests that heluoshugan capsule might have therapeutic effect on liver fibrosis induced by the infection of Schistosoma japonicum in mice, by inhibiting the activation of hepatic stellate cells and the pathological change of liver blood vessel.

Possible associations of rectal carcinoma with Schistosoma japonicum infection and membranous nephropathy: a case report with a review.

We report the first case of rectal carcinoma associated with S. japonicum and membranous nephropathy. A 57-year-old Japanese man noticed narrowing of his feces. He had lived in Yamanashi prefecture, an endemic area of S. japonicum. He had suffered from nephrotic syndrome for about 1 year. Barium enema study showed a severe stricture in the upper rectum and biopsy specimens from the tumor demonstrated well differentiated adenocarcinoma and many ova of S. japonicum. Sonography of the liver showed a network pattern and a linear high echoic area. Low anterior resection with incisional biopsy of the liver and the right kidney was performed. Histopathological findings showed well differentiated adenocarcinoma and schistosomal ova. The total number of ova in the resected colon amounted to 15,133, consisting of 2243 inside and 12,890 outside the carcinoma. The nearer to the carcinoma the area was, the higher was the density of ova. The findings of light microscopy and electron microscopy of the biopsy specimen from the kidney were compatible with membranous nephropathy (stage II). This case suggests that schistosomal ova have some effect on carcinogenesis and nephrotic syndrome. In patients with nephrotic syndrome of unknown cause, especially in inhabitants of endemic areas of S. japonicum, gastrointestinal malignancy should be ruled out as an etiological factor. Sigmoidoscopy would be useful for colorectal carcinoma surveillance in S. japonicum patients.

[A case of colon cancer associated with schistosomiasis japonica].

A case of colon cancer associated with schistosomiasis japonica is reported. A 60-year-old man was admitted with the complaint of melena. Barium enema study revealed a colon tumor (type 1') 11 cm from the anal ring. Sigmoidectomy was performed, and no lymph node metastasis was observed. Histologically, the tumor was diagnosed as well-differentiated adenocarcinoma, and also many schistosoma ova were found not only in the lesion of the carcinoma, but also in the tissue surrounding the carcinoma. In the latter lesion, ova were observed beneath muscularis mucosae. The distributions of the ova in the anal side of the tumor were more dominant than those in oral side. We review the direct correlation between gastrointestinal tract cancer and the schistosomiasis japonica in other reports.