Silymarin treatment reduces granuloma and hepatic fibrosis in experimental schistosomiasis

Hilton, Mata-Santos; Lino, Fabiana Gonçalves; Rocha, Carolina Carneiro; Paiva, Cláudia N.; Branco, Morgana Teixeira Lima Castelo; Pyrrho, Alexandre dos Santos

doi:10.1007/s00436-010-2014-8

Cited by 34 publications

(37 citation statements)

References 35 publications

(30 reference statements)

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“…We have previously demonstrated that silymarin reduces granuloma area and collagen deposition during acute S. mansoni infection (8). It has been previously demonstrated that other antioxidants also have the ability to prevent schistosomiasis-induced fibrosis when adminis- tered in the acute phase (4,5).…”

Section: Discussionmentioning

confidence: 99%

“…Silymarin was suspended in 1% carboxymethylcellulose (CMC) (Sigma-Aldrich, USA) (25,26) to avoid quick precipitation and administered every 48 h at 10 mg kg Ϫ1 of body weight intraperitoneally (i.p.) as previously described (8). Noninfected controls (N) and infected (I) mice were divided randomly in seven groups of 8 animals: nontreated (N and I), treated during 80 days with CMC (IϩVeh 80D), or treated with silymarin for 80 days (NϩSIL 80D and IϩSIL 80D), 50 days (IϩSIL 50D), or 10 days (IϩSIL 10D).…”

Section: Methodsmentioning

confidence: 99%

“…We have previously demonstrated that silymarin administration reduces fibrosis deposition in the liver during acute S. mansoni infection. This reduction is associated with a decrease in granuloma sizes (8).…”

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confidence: 97%

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Silymarin Reduces Profibrogenic Cytokines and Reverses Hepatic Fibrosis in Chronic Murine Schistosomiasis

Hilton

Dutra

Rocha

et al. 2014

Antimicrob Agents Chemother

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In chronic schistosomiasis, hepatic fibrosis is linked to the portal hypertension that causes morbidity in Schistosoma mansoni infection. Silymarin (SIL) is a hepatoprotective and antioxidant medicament largely prescribed against liver diseases that has previously been shown to prevent fibrosis during acute murine schistosomiasis. Here we employed silymarin to try to reverse established hepatic fibrosis in chronic schistosomiasis. Silymarin or vehicle was administered to BALB/c mice every 48 h, starting on the 40th (80 days of treatment), 70th (50 days), or 110th (10 days) day postinfection (dpi). All mice were sacrificed and analyzed at 120 dpi. Treatment with silymarin reduced liver weight and granuloma sizes, reduced the increase in alanine aminotransferase and aspartate aminotransferase levels, and reduced the established hepatic fibrosis (assessed by hydroxyproline contents and picrosirius staining). Treatment with silymarin also reduced the levels of interleukin-13 (IL-13) in serum and increased the gamma interferon (IFN-␥)/IL-13 ratio. There was a linear correlation between IL-13 levels in serum and hydroxyproline hepatic content in both infected untreated and SIL-treated mice, with decreased IL-13 levels corresponding to decreased hydroxyproline hepatic contents. Treatment with either SIL or N-acetylcysteine reduced both proliferation of fibroblast cell lines and basal/IL-13-induced production of collagen I, indicating that besides inhibiting IL-13 production during infection, SIL antioxidant properties most likely contribute to inhibition of collagen production downstream of IL-13. These results show that silymarin interferes with fibrogenic cytokines, reduces established fibrosis, and inhibits downstream effects of IL-13 on fibrogenesis, indicating the drug as a safe and cheap treatment to liver fibrotic disease in schistosomiasis. Schistosomiasis is a chronic disease of high prevalence and wide distribution around the world (1) caused by worms that parasitize the vascular system. The morbidity in schistosomiasis is associated with the arrival of worm eggs to the liver and the stimulation of a granulomatous reaction (2). Chronic liver pathology is closely associated to the nature of the host inflammatory response. The immunological progression of this disease is frequently divided in distinct phases: prepostural acute Th1 phase, postural acute Th2 phase, and chronic Th2 downmodulated phase (3). The control of this Th response throughout the chronic phase may be associated with the reduction of morbidity in schistosomiasis. During acute murine infection, administration of antioxidant drugs such as curcumin (4), resveratrol (5), n-acetylcysteine (6), artemether (7), and silymarin (8) is used to reduce morbidity and prevent hepatic fibrosis. The reversal of established hepatic fibrosis at the chronic stage is directly linked to the portal hypertension, the major cause of morbidity in Schistosoma mansoni infection, and was not attained in any of these previous works. Currently, there is no medical treatmen...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Silymarin Reduces Profibrogenic Cytokines and Reverses Hepatic Fibrosis in Chronic Murine Schistosomiasis

Hilton

Dutra

Rocha

et al. 2014

Antimicrob Agents Chemother

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“…Silibinin (SBN) is the major active substituent of silymarin. Silymarin currently is used successfully for liver disorders and also as an anticancer and anti-inflammatory agent [Anjeli et al 2010;Mata-Santos et al 2010]. It acts as a potent antioxidant by reacting with ROS, and also potentiates the effects of the physiological antioxidants such as glutathione and superoxide dismutase [El-Shitany et al 2008;Nencini et al 2007].…”

Section: Introductionmentioning

confidence: 99%

Silymarin protects from varicocele-induced damages in testis and improves sperm quality: evidence for E2f1 involvement

Moshtaghion¹,

Malekinejad²,

Razi

et al. 2013

Systems Biology in Reproductive Medicine

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This study was designed to evaluate the protective effect of silymarin (SMN) on varicocele-induced damage in testis and its effects on sperm parameters and on antioxidant status. Wistar rats were divided into three groups: control-sham, varicocele-induced, and SMN-treated varicocelized (50mg/kg, orally) rats. The sperm count, DNA integrity, and histone-protamine transition was evaluated after 42 days. The antioxidant status was analyzed by determining testicular malondialdehyde (MDA) and total thiol molecules (TTM). The endocrine status of the testicular tissue was estimated by counting the normal Leydig cell distribution/mm 2 and by determination of serum testosterone. The expression of E2f1 mRNA was analyzed using RT-PCR. Carbohydrate depletion and lipid foci replacement in germinal cells were examined by histochemical analyses. Silymarin rehabilitated the varicocele-induced Leydig cell degeneration and testosterone reduction. In addition, SMN recovered the varicocele-induced reduction of TTM and lowered significantly (P < 0.05) the varicocele-elevated content of MDA. The SMN treatment resulted in a significant (P < 0.05) down-regulation of the VCL-up-regulated E2f1 mRNA. Silymarin-treated animals were protected from varicoceleinduced testicular atrophy and these animals showed a significant (P < 0.05) increase in the percentage of seminiferous tubules with positive tubular differentiation, repopulation, and spermiogenesis indices. Furthermore, SMN improved the varicocele-induced carbohydrate reduction in germinal cells. Our data suggest that in addition to oxidative stress, alteration in the testicular endocrine function plays a crucial role in the pathogenesis of varicocele. Moreover, the protective effects of SMN on varicocele-induced damage may reflect its antioxidant property, which may be mediated via the E2f1 transcription factor.

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“…This effect could be attributed to its role as an antioxidant, antifibrotic, and antiinflammatory/immunomodulatory agent (Mata-Santos et al 2010). Mata-Santos et al (2014) showed that treatment with silymarin leads to a decrease in hepatic granulomas size and to a reduction in liver fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Cytokine patterns in experimental schistosomiasis mansoni infected mice treated with silymarin

et al. 2014

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The purpose of this study was to determine cytokine patterns in experimental schistosomiasis mansoni infected mice treated with silymarin. The study was conducted upon 100 mice that were divided into five groups; 20 each: uninfected control group, Schistosoma mansoni infected untreated mice (infected control), infected mice treated with praziquantel (PZQ), infected mice treated with silymarin and infected mice treated with both praziquantel and silymarin. 10 mice from each group were sacrificed at 10th and 18th weeks post infection respectively. Histopathological investigations were performed. Liver sections were stained with hematoxylin-eosin and Masson's trichrome stain to evaluate changes of granuloma sizes and numbers. Serum levels of the cytokines (TNF-a, IFN-c, IL-4 and TGF-b1) were assessed in the sera of all groups by immunoassay. The measured levels of cytokines (IFN-c, IL-4, TNF-a, TGF-b1) were found to be significantly increased in infected mice compared to normal control. At the same time, treated groups with silymarin alone or combined with PZQ showed significant decrease in IL-4, TNF-a and TGF-b1 levels compared to infected control. On the other hand, there was a significant increase in IFN-c level observed in all treated groups compared to infected control. In addition, the histopathological examination of the liver in the group treated with PZQ showed a reduction in the number of livers eggs granuloma at all periods of sacrification compared with the infected untreated group. However, there was more decrease in granulomas diameter in both silymarin treated group or combined with PZQ at all periods of sacrification when compared to infected untreated group. In conclusion; treatment with silymarin combined with PZQ in murine schistosomiasis could reduce hepatic fibrosis by their action on the production of pro-inflammatory cytokines.

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Silymarin treatment reduces granuloma and hepatic fibrosis in experimental schistosomiasis

Cited by 34 publications

References 35 publications

Silymarin Reduces Profibrogenic Cytokines and Reverses Hepatic Fibrosis in Chronic Murine Schistosomiasis

Silymarin Reduces Profibrogenic Cytokines and Reverses Hepatic Fibrosis in Chronic Murine Schistosomiasis

Silymarin protects from varicocele-induced damages in testis and improves sperm quality: evidence for E2f1 involvement

Cytokine patterns in experimental schistosomiasis mansoni infected mice treated with silymarin

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