The Role of Praziquantel in the Prevention and Treatment of Fibrosis Associated with Schistosomiasis: A Review

Niu, Xuehua; Hu, Tao; Hong, Ye; Li, Xiaoyan; Shen, Yuzhou

doi:https://doi.org/10.1155/2022/1413711

Journal of Tropical Medicine

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Abstract Introduction Conclusions Data Availability Conflicts of Interest Acknowledgments References Copyright Related Articles

Review Article | Open Access

Volume 2022 | Article ID 1413711 | https://doi.org/10.1155/2022/1413711

The Role of Praziquantel in the Prevention and Treatment of Fibrosis Associated with Schistosomiasis: A Review

Xuehua Niu,¹Tao Hu,¹Ye Hong,¹Xiaoyan Li,¹and Yuzhou Shen¹

Academic Editor: Wei Wang

Received15 Aug 2022

Revised05 Oct 2022

Accepted12 Oct 2022

Published21 Oct 2022

Abstract

Schistosomiasis remains a major global public health concern. Currently, the control of this neglected tropical disease still depends on chemotherapy to reduce the prevalence and intensity of the parasite infection. It has been widely accepted that praziquantel is highly effective against all species of Schistosoma, and this agent is virtually the only drug of choice for the treatment of human schistosomiasis. Mass drug administration (MDA) with praziquantel has been shown to be effective in greatly reducing the prevalence and morbidity due to schistosomiasis worldwide. In addition to antischistosomal activity, a large number of experiential and clinical evidence has demonstrated the action of praziquantel against fibrosis caused by S. mansoni and S. japonicum infections through decreasing the expression of fibrotic biomarkers such as α-smooth muscle actin (α-SMA), collagen, matrix metalloproteinase (MMP), and tissue inhibitor of metalloproteinase (TIMP), and inhibiting the expression of proinflammatory cytokines such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β, as well as chemokines, and similar antifibrotic activity was observed in mouse models of fibrosis induced by carbon tetrachloride (CCl4) and concanavalin A (Con-A). In this review, we discuss the role of praziquantel in the prevention and treatment of fibrosis associated with schistosomiasis and the possible mechanisms. We call for randomized, controlled clinical trials to evaluate the efficacy and safety of praziquantel in the treatment of schistosomiasis-induced hepatic fibrosis, and further studies to investigate the potential of praziquantel against fibrosis associated with alcohol consumption, viruses, and toxins seem justified.

1. Introduction

Schistosomiasis, a neglected tropical disease caused by the blood fluke of the genus Schistosoma, remains a global public health concern that ranks second to malaria among human parasitic diseases in terms of the number of people infected and at risk of infection [1]. Worldwide, it is estimated that over 140 million people are thought to have the disease, with a further 779 million at risk of infection [2]. Although the elimination of this tropical parasitic disease requires a multidisciplinary integrated approach [3–5], the control of schistosomiasis still relies on chemotherapy, which has been proven to be effective in reducing the prevalence and intensity of the parasitic infection [6–8].

Hepatosplenic schistosomiasis is characterized by typical pathological changes at chronic and advanced stages, including egg granulomas, fibrosis, and tissue damage within the liver and other host tissues [1]. Hepatic fibrosis, which is characterized by excessive deposition of collagen and other extracellular matrix (ECM) components resulting from granulomatous responses triggered by soluble egg antigens (SEA) secreted by parasite eggs, is the main pathological mechanism and the major lesion of hepatosplenic schistosomiasis [9]. Hepatic stellate cells (HSCs), hepatic macrophages, immune cells, cytokines (interleukin (IL)-13, transformation growth factor (TGF)-β1, interferon (IFN)-γ), and microRNAs (miRNAs) have been found to contribute to the pathogenesis of schistosomiasis-induced hepatic fibrosis [10–17]. Portal hypertension and ascites associated with hepatic fibrosis have been identified as the main causes of mortality among patients with chronic hepatosplenic schistosomiasis [18], and currently, there is no cure for hepatic fibrosis except liver transplantation [19]. However, liver transplantation suffers from problems of lack of donors, high costs, and use of immunosuppressive agents, which limits its clinical applications [20]. A search for novel treatments for hepatic fibrosis is therefore given a high priority.

Since praziquantel, a broad-spectrum schistosomicide, was developed in 1970 s [21], it has replaced other antischistosomal agents to become the only drug of choice for treatment of human schistosomiasis due to high efficacy, low toxicity, easy administration, and low cost [22–24]. The agent is found to be active against all species of Schistosoma, notably, adult stages of the parasite [25]. As a consequence, the introduction of praziquantel led to the global schistosomiasis control strategy shifting from disease control to morbidity control [26]. Mass drug administration (MDA) with praziquantel has been shown to be effective in reducing the prevalence and morbidity due to schistosomiasis [27–29]. Furthermore, an antifibrotic activity of praziquantel was reported in both animal models and patients infected with schistosomiasis [30,31]. This review article aims to discuss the role of praziquantel in the prevention and control of fibrosis associated with schistosomiasis and the possible mechanisms.

2. Literature Search Strategy

A joint search was performed in international and national electronic databases, including Web of Knowledge, PubMed, Scopus, Google Scholar, Wanfang Data (https://www.wanfangdata.com.cn/), CNKI (https://www.cnki.net) and VIP (https://qikan.cqvip.com/) using the terms “schistosomiasis,” “fibrosis,” and “praziquantel” to retrieve publications concerning the action of praziquantel against fibrosis associated with schistosomiasis during the period from January 1st, 1970 to December 31st, 2021. Inclusion criteria involved: (1) studies reporting the activity of praziquantel against fibrosis associated with schistosomiasis; and (2) animal studies or clinical reports. Publications that met the following exclusion criteria were: (1) review articles; or (2) the full text was unavailable.

2.1. Experimental Evidence

In a murine model of S. mansoni-induced hepatic fibrosis, administration of praziquantel at a dose of 250 mg/kg modestly diminished liver fibrosis as compared to untreated controls 10 weeks post-treatment and suppressed fibrosis and reduced liver collagen content to normal levels 20 weeks post-treatment [32]. In Swiss albino mice experimentally infected with S. mansoni, praziquantel treatment resulted in a reduction in total collagen content and a recovery of the type III (Col3)/I collagen (Col1) ratio to normal limits [33]. In Syrian golden hamsters infected with 100 S. mansoni cercariae each, a significant reduction in hepatic and splenic granulomas, fibrosis, and circulating cathodic antigen (CCA), and circulating anodic antigen (CAA) was seen following praziquantel treatment [34]. Following praziquantel administration, amelioration of hepatic granulomas and reduction of Col1, Col3, and Col4 gene expression were observed 6 and 12 months post-treatment, and 71.4% resorption of hepatic fibrous tissues was found 12 months post-treatment in a CBA/J^k mouse model of S. mansoni infections [35]. In Swiss Webster outbred mice infected with S. mansoni, treatment with praziquantel resulted in elimination of egg granulomas or collagen fibrils, and reduced the expression of signal transducer and activator of transcription 1 (STAT1), STAT4, IFN-γ, TBET, IL-4, C–C motif chemokine ligand 12 (CCL12), and CCL22 [36]. In addition, treatment with praziquantel at a dose of 80 mg/kg 50 days postinfection for 5 consecutive days was reported to result in a significant reduction in the volume density of hepatocytes, sinusoids, and hepatic fibrosis in mice infected with S. mansoni and fed either a low-protein diet (8% protein) or standard chow (22% protein) [37]. In a recent study, however, treatment with praziquantel at a dose of 400 mg/kg twice daily 12 weeks postinfection for a week followed by praziquantel treatment at a dose of 400 mg/kg twice daily for 4 weeks was found to achieve comparable collagen deposition, hydroxyproline level, and granuloma areas relative to untreated controls in the murine model of chronic experimental schistosomiasis mansoni [38] (Table 1).

In addition, combined therapy of praziquantel with alpha lipoic acid [39], silymarin [40], AT1 receptor antagonist losartan [41], was reported to achieve a greater activity against hepatic fibrosis induced by S. mansoni infection than praziquantel monotherapy. Since stem cell therapy has shown a potential value in treatment of schistosomiasis-associated fibrosis [42–44], the antifibrotic activity of human Wharton's jelly-derived mesenchymal stem cells in combination with praziquantel was evaluated in S. mansoni-infected mice, and the combination was found to achieve a higher beneficial efficacy against S. mansoni-induced liver fibrosis than monotherapy with mesenchymal stem cells or praziquantel alone, as revealed by histopathological, morphometric, and gelatin zymographic results as well as reduction of alpha smooth muscle actin (α-SMA), Col1, and IL-13 expression [45].

In animal models of fibrosis induced by S. japonicum, praziquantel treatment was found to reduce serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations, the areas of egg granulomas, areas of collagen deposition and hepatic hydroxyproline contents, alleviate fibrotic proliferation, inflammatory infiltration, hepatocyte degeneration and necrosis, improve liver size and texture, decrease the levels of fibrosis-related parameters including α-SMA, SPET4, matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1, Col1α1, and Col3α1 in relative to infected but untreated controls, and inhibit the expression of proinflammatory cytokines tumor necrosis factor (TNF)-α and TGF-β1[31, 46–52] (Table 2). Combined treatment with praziquantel and IFN-γ was reported to result in a greater decline in hepatic fibrosis score and area of collagen deposition, higher reduction of Col1 and Col3 expression, more downregulation of Smad2 expression and upregulation of Smad7 expression as compared to treatment with praziquantel alone [53, 54], and the combination of praziquantel and the Amusium pleuronectes polysaccharide presented a more inhibitory effect on hepatic fibrosis than treatment with praziquantel or the polysaccharide alone in S. japonicum-infected mice, as revealed by lower Col1, Col2, and Col4 levels, lower parasite egg burdens and higher IL-12 and IFN-γ productions [55]. In addition, combining praziquantel and extracts from traditional Chinese medicines achieved synergistic activity in the treatment of S. japonicum-induced hepatic fibrosis [56–58].

The results of these experimental studies demonstrate the effectiveness of praziquantel against hepatic fibrosis induced by S. mansoni or S. japonicum infection, which encourages the randomized, controlled clinical trials to confirm the antifibrotic activity of praziquantel.

2.2. Exciting Findings from Human Trials

To date, there are no randomized, controlled trials to examine the role of praziquantel in prevention and control of fibrosis associated with schistosomiasis; however, available data have shown the antifibrotic value of praziquantel in treatment of patients with schistosomiasis-induced fibrosis [30, 59]. In S. mansoni-infected subjects, administration of praziquantel at a total dose of 40 or 50 mg/kg resulted in improvements in the ultrasonographic parameters of fibrosis [60–64] (Table 3). Among S. japonicum-infected patients, praziquantel treatment at a total dose of 40 or 60 mg/kg was found to improve the ultrasonographic and biochemical parameters in patients with mild fibrosis but not in patients with severe fibrosis [30, 65–68] (Table 4); however, Fabre and colleagues reported an elevated prevalence of hepatic fibrosis in S. japonicum-infected Filipinos following one-year treatment of praziquantel at a total dose of 60 mg/kg given in a split dose [69]. Furthermore, multicenter, randomized, double-blind, and controlled clinical trials are required to validate the antifibrotic efficacy of praziquantel.

2.3. Mechanisms Underlying Antifibrotic Activity of Praziquantel against Schistosoiasis-Induced Fibrosis

Previous studies have demonstrated that praziquantel is active against schistosomiasis-induced hepatic fibrosis through decreasing the expression of fibrotic biomarkers including α-SMA, collagen, MMP, and TIMP, and inhibiting the expression of proinflammatory cytokines such as IL-6, TNF-α, and TGF-β, as well as chemokines [31–34, 47–52]. In addition, praziquantel treatment resulted in a high proportion of the active form of the interstitial collagenase [70], inhibition of SEPT4 expression at both translational and transcriptional levels [48], and increased plasminogen activator activity [71], which was considered to contribute to the reversal of schistosomiasis-induced fibrosis. Since multiple factors are involved in schistosomiasis-induced fibrosis, the exact mechanisms underlying the action of praziquantel against schistosomiasis-induced fibrosis require further investigations.

3. Conclusions and Perspectives

Currently, there are no effective treatments for hepatic fibrosis except liver transplantation [19]. Early diagnosis and interventions are of great importance to attenuate hepatic fibrosis; however, there are still challenges for early diagnosis of hepatic fibrosis [72]. Nevertheless, artificial intelligence (AI) opens the new era of precision medicine in hepatology, which facilitates early precise identification and prediction of disease severity and progression, the presence of complications, and outcomes of hepatic fibrosis [73–75]. In addition, stem cell therapy has shown great potential in the treatment of hepatic fibrosis, which provides a new hope for the treatment of hepatic fibrosis [76–78]; however, further prospective clinical trials to examine the efficacy and safety of stem cell therapy for hepatic fibrosis associated with schistosomiasis are required.

It has been proven that praziquantel is a highly effective and mildly toxic schistosomicide [79], and praziquantel-based chemotherapy has been widely implemented in the national schistosomiasis control program around the world and plays a great role in the transmission of schistosomiasis [80]. In addition to antischistosomal action, both experimental studies and clinical trials have revealed the antifibrotic activity of praziquantel against hepatic fibrosis induced by S. japonicum and S. mansoni infection [47–52,61–68]. Moreover, oral administration of praziquantel at a dose of 300 mg/kg given twice daily for 30 days resulted in a significant reduction of the collagen areas, content of hepatic hydroxyproline, and serum ALT and AST levels in a CCl₄-induced mouse model of hepatic fibrosis [30]. In the concanavalin A (Con A)-induced model of hepatic fibrosis, praziquantel was also found to improve the morphological and biochemical parameters associated with hepatic fibrosis [81]. Since hepatic fibrosis may be induced by virus, alcohol and toxin [82–84], and there are millions of subjects suffering from hepatic fibrosis due to viral hepatitis, parasitic diseases, toxic chemicals, and alcohol consumption, further studies to investigate the potential of praziquantel against alcoholic, viral, and toxin-induced fibrosis seem justified.

In summary, praziquantel, an old schistosomicide, is a promising antifibrotic drug. Although randomized, controlled clinical trials are required to validate the antifibrotic action, and there are still a large number of challenges ahead, the antifibrotic activity of praziquantel may benefit thousands of patients, due to its low cost, easy administration, and low toxicity. In addition, the timing, dosing, optimal regimens, and mechanisms of action of praziquantel for treatment of fibrosis require further investigation.

Data Availability

All data presented in this study are available from the corresponding author upon request.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Acknowledgments

This study was financially supported by the Jiangsu Provincial Association of Endemic Diseases (grant no. X202107) and the Key Specialty Discipline of Kunshan City.

References

D. P. McManus, D. W. Dunne, M. Sacko, J. Utzinger, B. J. Vennervald, and X. N. Zhou, Nature Reviews Disease Primers, vol. 4, no. 1, p. 13, 2018.
View at: Publisher Site
A. K. Deol, F. M. Fleming, B. Calvo-Urbano et al., “Schistosomiasis - assessing progress toward the 2020 and 2025 global goals,” New England Journal of Medicine, vol. 381, no. 26, pp. 2519–2528, 2019.
View at: Publisher Site | Google Scholar
L. L. Wu, H. H. Hu, X. Zhang et al., “Cost-effectiveness analysis of the integrated control strategy for schistosomiasis japonica in a lake region of China: a case study,” Infect Dis Poverty, vol. 10, no. 1, p. 79, 2021.
View at: Publisher Site | Google Scholar
H. D. Mazigo, “Participatory integrated control strategies and elimination of schistosomiasis in sub-Saharan Africa,” Lancet Global Health, vol. 7, no. 8, pp. e998–e999, 2019.
View at: Publisher Site | Google Scholar
C. Qian, Y. Zhang, X. Zhang et al., “Effectiveness of the new integrated strategy to control the transmission of Schistosoma japonicum in China: a systematic review and meta-analysis,” Parasite, vol. 25, p. 54, 2018.
View at: Publisher Site | Google Scholar
C. Kokaliaris, A. Garba, M. Matuska et al., “Effect of preventive chemotherapy with praziquantel on schistosomiasis among school-aged children in sub-Saharan Africa: a spatiotemporal modelling study,” The Lancet Infectious Diseases, vol. 22, no. 1, pp. 136–149, 2022.
View at: Publisher Site | Google Scholar
P. Ogongo, R. K. Nyakundi, G. K. Chege, and L. Ochola, “The road to elimination: current state of schistosomiasis research and progress towards the end game,” Frontiers in Immunology, vol. 13, Article ID 846108, 2022.
View at: Publisher Site | Google Scholar
H. C. Turner, W. A. Stolk, A. W. Solomon et al., “Are current preventive chemotherapy strategies for controlling and eliminating neglected tropical diseases cost-effective?” BMJ Glob Health, vol. 6, no. 8, Article ID e005456, 2021.
View at: Publisher Site | Google Scholar
Z. A. Andrade, “Schistosomiasis and liver fibrosis,” Parasite Immunology, vol. 31, no. 11, pp. 656–663, 2009.
View at: Publisher Site | Google Scholar
J. P. Carson, G. A. Ramm, M. W. Robinson, D. P. McManus, and G. N. Gobert, “Schistosome-induced fibrotic disease: the role of hepatic stellate cells,” Trends in Parasitology, vol. 34, no. 6, pp. 524–540, 2018.
View at: Publisher Site | Google Scholar
D. Cheng, J. Chai, H. Wang, L. Fu, S. Peng, and X. Ni, “Hepatic macrophages: Key players in the development and progression of liver fibrosis,” Liver International, vol. 41, no. 10, pp. 2279–2294, 2021.
View at: Publisher Site | Google Scholar
E. Huang, N. Peng, F. Xiao, D. Hu, X. Wang, and L. Lu, “The roles of immune cells in the pathogenesis of fibrosis,” International Journal of Molecular Sciences, vol. 21, no. 15, p. 5203, 2020.
View at: Publisher Site | Google Scholar
T. A. Wynn, “Cellular and molecular mechanisms of fibrosis,” The Journal of Pathology, vol. 214, no. 2, pp. 199–210, 2008.
View at: Publisher Site | Google Scholar
J. Li, W. Wang, and J. L. Shen, “The role of TGFbeta1 and IL-13 in cellular signal transduction of hepatic fibrosis of schistosomiasis,” Chinese Journal of Parasitology & Parasitic Diseases, vol. 27, no. 4, pp. 357–360, 2009.
View at: Google Scholar
L. Yu, X. Sun, F. Yang, J. Yang, J. Shen, and Z. Wu, “Inflammatory cytokines IFN-γ, IL-4, IL-13 and TNF-α alterations in schistosomiasis: a meta-analysis,” Parasitology Research, vol. 110, no. 4, pp. 1547–1552, 2012.
View at: Publisher Site | Google Scholar
Z. Zhao, C. Y. Lin, and K. Cheng, “siRNA- and miRNA-based therapeutics for liver fibrosis,” Translational Research, vol. 214, pp. 17–29, 2019.
View at: Publisher Site | Google Scholar
S. Ghafouri-Fard, A. Abak, S. F. Talebi et al., “Role of miRNA and lncRNAs in organ fibrosis and aging,” Biomedicine & Pharmacotherapy, vol. 143, Article ID 112132, 2021.
View at: Publisher Site | Google Scholar
A. Altamirano-Barrera, B. Barranco-Fragoso, and N. Méndez-Sánchez, “Management strategies for liver fibrosis,” Annals of Hepatology, vol. 16, no. 1, pp. 48–56, 2017.
View at: Publisher Site | Google Scholar
L. Shan, F. Wang, D. Zhai, X. Meng, J. Liu, and X. Lv, “New drugs for hepatic fibrosis,” Frontiers in Pharmacology, vol. 13, Article ID 874408, 2022.
View at: Publisher Site | Google Scholar
J. F. Trotter, “Current issues in liver transplantation,” Gastroenterology and Hepatology, vol. 12, no. 4, pp. 214–219, 2016.
View at: Google Scholar
R. Gönnert and P. Andrews, “Praziquantel, a new board-spectrum antischistosomal agent,” Zeitschrift Fuer Parasitenkunde, vol. 52, no. 2, pp. 129–150, 1977.
View at: Publisher Site | Google Scholar
M. S. Berhanu, S. A. Atnafie, T. E. Ali, A. A. Chekol, and H. B. Kebede, “Efficacy of praziquantel treatment and Schistosoma mansoni infection among primary school children in Kemisse Town, Northeast Ethiopia,” Ethiopia Journal of Health Science, vol. 32, no. 3, pp. 631–640, 2022.
View at: Publisher Site | Google Scholar
P. Makaula, S. A. Kayuni, K. C. Mamba et al., “An assessment of implementation and effectiveness of mass drug administration for prevention and control of schistosomiasis and soil-transmitted helminths in selected southern Malawi districts,” BMC Health Services Research, vol. 22, no. 1, p. 517, 2022.
View at: Publisher Site | Google Scholar
T. Spangenberg, “Alternatives to praziquantel for the prevention and control of schistosomiasis,” ACS Infectious Diseases, vol. 7, no. 5, pp. 939–942, 2021.
View at: Publisher Site | Google Scholar
M. Fukushige, M. Chase-Topping, M. E. J. Woolhouse, and F. Mutapi, “Efficacy of praziquantel has been maintained over four decades (from 1977 to 2018): a systematic review and meta-analysis of factors influence its efficacy,” PLoS Neglected Tropical Diseases, vol. 15, no. 3, Article ID e0009189, 2021.
View at: Publisher Site | Google Scholar
D. M. Cribb, N. E. Clarke, S. A. R. Doi, and S. Vaz Nery, “Differential impact of mass and targeted praziquantel delivery on schistosomiasis control in school-aged children: a systematic review and meta-analysis,” PLoS Neglected Tropical Diseases, vol. 13, no. 10, Article ID e0007808, 2019.
View at: Publisher Site | Google Scholar
H. C. Turner, J. E. Truscott, F. M. Fleming, T. D. Hollingsworth, S. J. Brooker, and R. M. Anderson, “Cost-effectiveness of scaling up mass drug administration for the control of soil-transmitted helminths: a comparison of cost function and constant costs analyses,” The Lancet Infectious Diseases, vol. 16, no. 7, pp. 838–846, 2016.
View at: Publisher Site | Google Scholar
Y. Camara, B. Sanneh, E. Joof et al., “Mapping survey of schistosomiasis and soil-transmitted helminthiases towards mass drug administration in the Gambia,” PLoS Neglected Tropical Diseases, vol. 15, no. 7, Article ID e0009462, 2021.
View at: Publisher Site | Google Scholar
M. Sangare, A. Berthe, H. Dolo et al., “Evaluation of mass drug administration for schistosomiasis and soil-transmitted helminths in school-aged children in Bankass, Mali,” International Journal of Infectious Diseases, vol. 112, pp. 196–201, 2021.
View at: Publisher Site | Google Scholar
W. Cai, Z. Chen, F. Chen, C. Zhou, R. Liu, and J. Wang, “Changes of ultrasonography and two serum biochemical indices for hepatic fibrosis in schistosomiasis japonica patients one year after praziquantel treatment,” Chinese Medical Journal, vol. 110, no. 10, pp. 797–800, 1997.
View at: Google Scholar
Y. J. Liang, J. Luo, Q. Yuan et al., “New insight into the antifibrotic effects of praziquantel on mice in infection with Schistosoma japonicum,” PLoS One, vol. 6, no. 5, Article ID e20247, 2011.
View at: Publisher Site | Google Scholar
S. H. Morcos, M. T. Khayyal, M. A. Dunn et al., “Reversal of hepatic fibrosis after praziquantel therapy of murine schistosomiasis,” The American Journal of Tropical Medicine and Hygiene, vol. 34, no. 2, pp. 314–321, 1985.
View at: Publisher Site | Google Scholar
N. M. el-Badrawy, H. I. Hassanein, S. S. Botros, F. M. Nagy, N. M. Abdallah, and D. Herbage, “Effect of praziquantel on hepatic fibrosis in experimental schistosomiasis mansoni,” Experimental and Molecular Pathology, vol. 49, no. 2, pp. 151–160, 1988.
View at: Publisher Site | Google Scholar
F. E. Moustafa, M. M. Hamouda, A. M. el-Shazly et al., “Effect of anti-schistosomal treatment on schistosomal hepatic pathology: an experimental study in Syrian golden hamsters,” Journal of the Egyptian Society of Parasitology, vol. 26, no. 2, pp. 517–524, 1996.
View at: Google Scholar
K. P. Singh, H. C. Gerard, A. P. Hudson, and D. L. Boros, “Expression of matrix metalloproteinases and their inhibitors during the resorption of schistosome egg-induced fibrosis in praziquantel-treated mice,” Immunology, vol. 111, no. 3, pp. 343–352, 2004.
View at: Publisher Site | Google Scholar
M. C. Sanchez, K. V. Krasnec, A. S. Parra et al., “Effect of praziquantel on the differential expression of mouse hepatic genes and parasite ATP binding cassette transporter gene family members during Schistosoma mansoni infection,” PLoS Neglected Tropical Diseases, vol. 11, no. 6, Article ID e0005691, 2017.
View at: Publisher Site | Google Scholar
L. A. Barros, M. Costa-Silva, C. L. Biolchini, R. H. Neves, and J. R. Machado-Silva, “Effect of praziquantel administration on hepatic stereology of mice infected with Schistosoma mansoni and fed a low-protein diet,” Brazilian Journal of Medical and Biological Research, vol. 42, no. 9, pp. 812–815, 2009.
View at: Publisher Site | Google Scholar
J. K. Nono, K. Fu, T. Mpotje et al., “Investigating the antifibrotic effect of the antiparasitic drug praziquantel in in vitro and in vivo preclinical models,” Scientific Reports, vol. 10, no. 1, Article ID 10638, 2020.
View at: Publisher Site | Google Scholar
E. H. Abdel-Hafeez, A. K. Ahmad, A. M. Abdulla, S. Aabdel-Wahab, and F. A. Mosalem, “Therapeutic effect of alpha lipoic acid combined with praziquantel on liver fibrosis induced by Schistosoma mansoni challenged mice,” Parasitology Research, vol. 111, no. 2, pp. 577–586, 2012.
View at: Publisher Site | Google Scholar
N. M. El-Lakkany, O. A. Hammam, W. H. El-Maadawy, A. A. Badawy, A. A. Ain-Shoka, and F. A. Ebeid, “Anti-inflammatory/anti-fibrotic effects of the hepatoprotective silymarin and the schistosomicide praziquantel against Schistosoma mansoni-induced liver fibrosis,” Parasites & Vectors, vol. 5, no. 1, p. 9, 2012.
View at: Publisher Site | Google Scholar
N. M. El-Lakkany, W. El-Maadawy, A. Ain-Shoka, A. Badawy, O. Hammam, and F. Ebeid, “Potential antifibrotic effects of AT1 receptor antagonist, losartan, and/or praziquantel on acute and chronic experimental liver fibrosis induced by Schistosoma mansoni,” Clinical and Experimental Pharmacology and Physiology, vol. 38, no. 10, pp. 695–704, 2011.
View at: Publisher Site | Google Scholar
M. M. El-Mahdi, W. A. Mansour, O. Hammam, N. A. Mehana, and T. M. Hussein, “Ameliorative effect of bone marrow-derived stem cells on injured liver of mice infected with Schistosoma mansoni,” Korean Journal of Parasitology, vol. 52, no. 2, pp. 151–162, 2014.
View at: Publisher Site | Google Scholar
H. Xu, H. Qian, W. Zhu et al., “Mesenchymal stem cells relieve fibrosis of Schistosoma japonicum-induced mouse liver injury,” Experimental Biology and Medicine (Maywood, NJ, United States), vol. 237, no. 5, pp. 585–592, 2012.
View at: Publisher Site | Google Scholar
B. B. Zhang, W. M. Cai, J. Tao, and X. F. Tang, “Effect of praziquantel and IFN-γ combined treatment on Smad protein expression in mice with hepatic fibrosis induced by Schistosoma japonicum infection,” Chinese Hepatology, vol. 19, no. 5, pp. 356–359, 2014.
View at: Google Scholar
O. A. Hammam, N. Elkhafif, Y. M. Attia et al., “Wharton's jelly-derived mesenchymal stem cells combined with praziquantel as a potential therapy for Schistosoma mansoni-induced liver fibrosis,” Scientific Reports, vol. 6, no. 1, Article ID 21005, 2016.
View at: Publisher Site | Google Scholar
H. Ohmae, K. Yasuraoka, T. Nara et al., “Serologic and ultrasonographic parameters of praziquantel treatment of hepatic fibrosis in Schistosoma japonicum infection,” The American Journal of Tropical Medicine and Hygiene, vol. 45, no. 3, pp. 350–359, 1991.
View at: Publisher Site | Google Scholar
H. L. Fang, J. J. Wang, M. Z. Chen, L. Jia, and C. W. Li, “Experimental study on praziquantel against schistosomiasis-induced hepatic fibrosis,” Shandong Medical Journal, vol. 50, no. 1, pp. 34-35, 2010.
View at: Google Scholar
D. Zhu, K. Song, J. Chen et al., “Expression of Septin4 in Schistosoma japonicum-infected mouse livers after praziquantel treatment,” Parasites & Vectors, vol. 8, no. 1, p. 19, 2015.
View at: Publisher Site | Google Scholar
P. Wei, D. D. Luo, L. J. Xiong, and L. L. Zeng, “Effects of praziquantel on the expression of hepatic Bcl-2 and Bax in schistosomiasis mice with liver fibrosis,” Chinese Journal of Parasitology Disease Control, vol. 18, no. 6, pp. 419–421, 2005.
View at: Google Scholar
L. J. Xiong, J. Zhu, and D. Luo, “Effects of praziquantel on the serous nitric oxide and intrahepatic induced nitric oxide synthase in schistosomiasis mice with liver fibrosis,” Chinese Journal of Integrated Traditional and Western Medicine, vol. 12, no. 2, pp. 153-154, 2002.
View at: Google Scholar
L. J. Xiong, S. Li, and D. Luo, “Effects of praziquantel on the serum level of cytokines in schistosomiasis mice with liver fibrosis,” Chinese Journal of Schistosomiasis Control, vol. 14, no. 5, pp. 369-370, 2002.
View at: Google Scholar
L. J. Xiong, D. Luo, and L. L. Zeng, “Effects of praziquantel on the expression of hepatic TGF-β1, type I and type III collagen in schistosomiasis mice with liver fibrosis,” Journal of Clinical International Medicine, vol. 20, no. 3, pp. 216-217, 2003.
View at: Google Scholar
F. Chen, W. M. Cai, and Z. Chen, “Effect of praziquntel and antifibrotic treatment on metabolism of collagen in liver fibrosis,” Chinese Journal of Infection Diseses, vol. 19, no. 5, pp. 355–358, 2001.
View at: Google Scholar
B. B. Zhang, Y. X. Chi, X. J. Chai, W. M. Cai, and T. Ju, “Studies on Smads at transcription level in liver fibrosis of mice with schistosomiasis japonica after treatment with praziquantel and interferon-gamma,” Chinese Journal Integration Traditional West Medicine, vol. 16, no. 4, pp. 295–298, 2008.
View at: Google Scholar
X. Tang, W. Hu, Y. Lv et al., “A polysaccharide from Amusium Pleuronectes combined with praziquantel treatment ameliorates hepatic fibrosis in Schistosoma japonicum-infected mice,” Medical Science Monitor, vol. 24, pp. 1597–1603, 2018.
View at: Publisher Site | Google Scholar
Y. Chen and Z. Xiao, “Therapeutic effect of resveratrol as well as resveratrol combined with praziquantel on the liver fibrosis due to Schistosoma japonicum infection in mice,” Chinese Journal of Parasitology & Parasitic Diseases, vol. 31, no. 5, pp. 337–341, 2013.
View at: Google Scholar
Z. H. Luo and B. Xu, “Effect of praziquantel and curcum in on expression of VEGF in liver fibrosis by Schistosoma japonicum infection,” Herald Medicine, vol. 27, no. 20, pp. 1164–1168, 2008.
View at: Google Scholar
Y. Y. Wu, S. S. He, and M. Deng, “Effects of combined use of aloeemodin and praziquantel on the transforming growth factor-β/Smad pathway in mice with schistosomiasis-induced liver fibrosis,” World Chinese Journal of Digestology, vol. 17, no. 27, pp. 2778–2783, 2009.
View at: Publisher Site | Google Scholar
X. Yuan and J. R. Dai, “Progress of researches on the actions of praziquantel against hepatic fibrosis,” Chinese Journal of Schistosomiasis Control, vol. 33, no. 5, pp. 540–543, 2021.
View at: Publisher Site | Google Scholar
N. Berhe, S. G. Gundersen, and B. Myrvang, “Reversibility of schistosomal periportal thickening/fibrosis after praziquantel therapy: a twenty-six month follow-up study in Ethiopia,” The American Journal of Tropical Medicine and Hygiene, vol. 78, no. 2, pp. 228–234, 2008.
View at: Publisher Site | Google Scholar
K. Frenzel, E. Doehring, E. Odongo-Aginya et al., “Evidence for a long-term effect of a single dose of praziquantel on Schistosoma mansoni-induced hepatosplenic lesions in northern Uganda,” The American Journal of Tropical Medicine and Hygiene, vol. 60, no. 6, pp. 927–931, 1999.
View at: Publisher Site | Google Scholar
P. Martins-Leite, G. Gazzinelli, L. F. Alves-Oliveira et al., “Effect of chemotherapy with praziquantel on the production of cytokines and morbidity associated with schistosomiasis mansoni,” Antimicrobial Agents and Chemotherapy, vol. 52, no. 8, pp. 2780–2786, 2008.
View at: Publisher Site | Google Scholar
R. Ruiz-Guevara, B. A. d. Noya, S. K. Valero, P. Lecuna, M. Garassini, and O. Noya, “Clinical and ultrasound findings before and after praziquantel treatment among Venezuelan schistosomiasis patients,” Revista da Sociedade Brasileira de Medicina Tropical, vol. 40, no. 5, pp. 505–511, 2007.
View at: Publisher Site | Google Scholar
E. I. Odongo-Aginya, T. L. Lakwo, and M. E. Doehring, “Evaluation of Schistosoma mansoni morbidity one year after praziquantel treatment in rhino cAMP and obongi in west nile, Uganda,” African Journal of Infectious Diseases, vol. 4, no. 2, pp. 43–50, 2010.
View at: Publisher Site | Google Scholar
Y. S. Li, A. C. Sleigh, A. G. Ross et al., “Two-year impact of praziquantel treatment for Schistosoma japnoicum infection in China: re-infection, subclinical disease and fibrosis marker measurements,” Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 94, no. 2, pp. 191–197, 2000.
View at: Publisher Site | Google Scholar
H. Ohmae, M. Tanaka, M. Hayashi et al., “Improvement of ultrasonographic and serologic changes in Schistosoma japnoicum-infected patients after treatment with praziquantel,” The American Journal of Tropical Medicine and Hygiene, vol. 46, no. 1, pp. 99–104, 1992.
View at: Publisher Site | Google Scholar
M. Tanaka, “The ultrasonographical and serological changes and their improvement after praziquantel treatment in Schistosoma japnoicum infected patients in Leyte, Philippines,” Memorias do Instituto Oswaldo Cruz, vol. 87, no. Suppl 4, pp. 277–280, 1992.
View at: Publisher Site | Google Scholar
L. Hong-Bao and S. Ming, “Efficacy of repeated application of praziquantel in treatment of hepatic fibrosis due to schistosomiasis,” Chinese Journal of Schistosomiasis Control, vol. 29, no. 2, pp. 241-242, 2016.
View at: Publisher Site | Google Scholar
V. Fabre, H. Wu, S. PondTor et al., “Tissue inhibitor of matrix-metalloprotease-1 predicts risk of hepatic fibrosis in human Schistosoma japonicum infection,” The Journal of Infectious Diseases, vol. 203, no. 5, pp. 707–714, 2011.
View at: Publisher Site | Google Scholar
H. Emonard and J. A. Grimaud, “Active and latent collagenase activity during reversal of hepatic fibrosis in murine schistosomiasis,” Hepatology, vol. 10, no. 1, pp. 77–83, 1989.
View at: Publisher Site | Google Scholar
J. Liu, D. Kong, J. Qiu et al., “Praziquantel ameliorates CCl4 -induced liver fibrosis in mice by inhibiting TGF-β/Smad signalling via up-regulating Smad7 in hepatic stellate cells,” British Journal of Pharmacology, vol. 176, no. 24, pp. 4666–4680, 2019.
View at: Publisher Site | Google Scholar
M. Lai and N. H. Afdhal, “Liver fibrosis determination,” Gastroenterology Clinics of North America, vol. 48, no. 2, pp. 281–289, 2019.
View at: Publisher Site | Google Scholar
T. H. Su, C. H. Wu, and J. H. Kao, “Artificial intelligence in precision medicine in hepatology,” Journal of Gastroenterology and Hepatology, vol. 36, no. 3, pp. 569–580, 2021.
View at: Publisher Site | Google Scholar
J. C. Ahn, A. Connell, D. A. Simonetto, C. Hughes, and V. H. Shah, “Application of artificial Intelligence for the diagnosis and treatment of liver diseases,” Hepatology, vol. 73, no. 6, pp. 2546–2563, 2021.
View at: Publisher Site | Google Scholar
C. Le Berre, W. J. Sandborn, S. Aridhi et al., “Application of artificial intelligence to gastroenterology and hepatology,” Gastroenterology, vol. 158, no. 1, pp. 76–94, 2020.
View at: Publisher Site | Google Scholar
M. Alsulami and R. Abdel-Gaber, “Cell therapy as a new approach on hepatic fibrosis of murine model of Schistosoma mansoni-infection,” Acta Parasitologica, vol. 66, no. 1, pp. 136–145, 2021.
View at: Publisher Site | Google Scholar
V. C. A. de Souza, D. M. N. Moura, M. C. A. B. de Castro et al., “Adoptive transfer of bone marrow-derived monocytes ameliorates Schistosoma mansoni-induced liver fibrosis in mice,” Scientific Reports, vol. 9, no. 1, p. 6434, 2019.
View at: Publisher Site | Google Scholar
Y. Zhang, J. Y. Mi, Y. J. Rui, Y. L. Xu, and W. Wang, “Stem cell therapy for the treatment of parasitic infections: is it far away?” Parasitology Research, vol. 113, no. 2, pp. 607–612, 2014.
View at: Publisher Site | Google Scholar
D. Cioli and L. Pica-Mattoccia, Parasitology Research, vol. 90, no. S1, pp. S3–S9, 2003.
View at: Publisher Site
A. F. Obe, “Praziquantel: do we need another antischistosoma treatment?” Future Medicinal Chemistry, vol. 7, no. 6, pp. 677–680, 2015.
View at: Publisher Site | Google Scholar
Q. Lu, Protection of Praziquantel against Concanavalin A-Induced Acute Liver Injury in Mice, Nanjing Medical University, Nanjing, China, 2013.
G. Gutierrez-Reyes, M. C. Gutierrez-Ruiz, and D. Kershenobich, “Liver fibrosis and chronic viral hepatitis,” Archives of Medical Research, vol. 38, no. 6, pp. 644–651, 2007.
View at: Publisher Site | Google Scholar
C. Liedtke, T. Luedde, T. Sauerbruch et al., “Experimental liver fibrosis research: update on animal models, legal issues and translational aspects,” Fibrogenesis & Tissue Repair, vol. 6, no. 1, p. 19, 2013.
View at: Publisher Site | Google Scholar
H. Tsukamoto, W. Horne, S. Kamimura et al., “Experimental liver cirrhosis induced by alcohol and iron,” Journal of Clinical Investigation, vol. 96, no. 1, pp. 620–630, 1995.
View at: Publisher Site | Google Scholar

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