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

2018 ◽  
Vol 55 (1) ◽  
pp. 21-32
Author(s):  
S. S. El-Hawary ◽  
K. F. Taha ◽  
F. N. Kirillos ◽  
A. A. Dahab ◽  
A. A. El-Mahis ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Schistosoma Mansoni ◽  
Hepatic Fibrosis ◽  
Colorimetric Assay ◽  
Quantitative Estimation ◽  
Scar Tissue ◽  
Egg Load ◽  
Total Polyphenols ◽  
Capparis Spinosa ◽  
Serum Aminotransferases

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

scholarly journals Preventive CTLA-4-Ig Treatment Reduces Hepatic Egg Load and Hepatic Fibrosis in Schistosoma mansoni-Infected Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Martina Sombetzki ◽  
Anne Rabes ◽  
Miriam Bischofsberger ◽  
Franziska Winkelmann ◽  
Nicole Koslowski ◽  
...  
Keyword(s):  
T Cell ◽  
Schistosoma Mansoni ◽  
Hepatic Fibrosis ◽  
T Cell Activation ◽  
Egg Production ◽  
Cell Activation ◽  
Cell Function ◽  
T Cell Response ◽  
Negative Regulator ◽  
Egg Load

Background. Hepatic fibrosis and granuloma formation as a consequence of tissue entrapped eggs produced by female schistosomes characterize the pathology of Schistosoma mansoni infection. We have previously shown that single-sex infection with female schistosomes mitigates hepatic fibrosis after secondary infection. This was associated with an increased expression of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), known as a negative regulator of T cell activation. Based on these findings, we hypothesized that administration of agonistic CTLA-4-Ig (Belatacept) is capable to prevent and/or treat hepatic fibrosis during schistosomiasis. Methods. Mice were infected with 50 S. mansoni cercariae and CTLA-4-Ig, or appropriated control-Ig was administered for 4 weeks. Preventive treatment started 4 weeks after infection, before onset of egg production, and therapeutic treatment started 8 weeks after infection when hepatic fibrosis was already established. Results. When given early after infection, livers of CTLA-4-Ig-treated mice showed significantly reduced collagen deposition and decreased expression of profibrotic genes in comparison to controls. In addition, administration of CTLA-4-Ig suppressed the inflammatory T cell response in infected mice. If therapy was started at a later time point when fibrogenesis was initiated, CTLA-4-Ig had no impact on hepatic fibrosis. Conclusion. We could demonstrate that an early preventive administration of CTLA-4-Ig suppresses effector T cell function and therefore ameliorates liver fibrosis. CTLA-4-Ig administration after onset of egg production fails to treat hepatic fibrosis.

scholarly journals Real-time monitoring of liver fibrosis through embedded sensors in a microphysiological system

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Hafiz Muhammad Umer Farooqi ◽  
Bohye Kang ◽  
Muhammad Asad Ullah Khalid ◽  
Abdul Rahim Chethikkattuveli Salih ◽  
Kinam Hyun ◽  
...  
Keyword(s):  
Cell Culture ◽  
Liver Fibrosis ◽  
Real Time ◽  
Hepatic Fibrosis ◽  
Transforming Growth Factor ◽  
Cell Monolayer ◽  
Embedded Sensors ◽  
Matrix Deposition ◽  
Tgf Β1

AbstractHepatic fibrosis is a foreshadowing of future adverse events like liver cirrhosis, liver failure, and cancer. Hepatic stellate cell activation is the main event of liver fibrosis, which results in excessive extracellular matrix deposition and hepatic parenchyma's disintegration. Several biochemical and molecular assays have been introduced for in vitro study of the hepatic fibrosis progression. However, they do not forecast real-time events happening to the in vitro models. Trans-epithelial electrical resistance (TEER) is used in cell culture science to measure cell monolayer barrier integrity. Herein, we explored TEER measurement's utility for monitoring fibrosis development in a dynamic cell culture microphysiological system. Immortal HepG2 cells and fibroblasts were co-cultured, and transforming growth factor β1 (TGF-β1) was used as a fibrosis stimulus to create a liver fibrosis-on-chip model. A glass chip-based embedded TEER and reactive oxygen species (ROS) sensors were employed to gauge the effect of TGF-β1 within the microphysiological system, which promotes a positive feedback response in fibrosis development. Furthermore, albumin, Urea, CYP450 measurements, and immunofluorescent microscopy were performed to correlate the following data with embedded sensors responses. We found that chip embedded electrochemical sensors could be used as a potential substitute for conventional end-point assays for studying fibrosis in microphysiological systems.

scholarly journals Total Antioxidant Capacity in HBV Carriers, a Promising Biomarker for Evaluating Hepatic Fibrosis: A Pilot Study

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 77
Author(s):  
Jing-Hua Wang ◽  
Sung-Bae Lee ◽  
Dong-Soo Lee ◽  
Chang-Gue Son
Keyword(s):  
Oxidative Stress ◽  
Chronic Hepatitis ◽  
Liver Fibrosis ◽  
Hepatitis B ◽  
Antioxidant Capacity ◽  
Chronic Hepatitis B ◽  
Hepatic Fibrosis ◽  
Total Antioxidant Capacity ◽  
Hbv Dna ◽  
Total Antioxidant

Oxidative stress plays a pivotal role in the progression of chronic hepatitis B; however, it is unclear whether the status of blood oxidative stress and antioxidant components differs depending on the degree of hepatic fibrosis. To explore the relationship between oxidative stress/antioxidant capacity and the extent of hepatic fibrosis, fifty-four subjects with liver fibrosis (5.5 ≤ liver stiffness measurement (LSM) score ≤ 16.0 kPa) by chronic hepatitis B virus (HBV) were analyzed. From the analysis of eight kinds of serum oxidative stress/antioxidant profiles and liver fibrosis degrees, the level of total antioxidant capacity (TAC) reflected a negative correlation with the severity of hepatic fibrosis (Pearson correlation, r = −0.35, p = 0.01). Moreover, TAC showed higher sensitivity (73.91%) than the aspartate transaminase (AST) to platelet ratio index (APRI, 56.52%) in the receiver operating characteristic (ROC) curves. Interestingly, the TAC level finely reflected the fibrosis degree in inactive carriers (HBV DNA < 2000 IU/mL), while the APRI did in active carriers (HBV DNA > 2000 IU/mL). In conclusion, TAC is a promising biomarker for evaluating the progression of liver fibrosis in patients with HBV, and this finding may indicate the involvement of TAC-composing factors in the pathogenesis of hepatic fibrosis in chronic HBV carriers.

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

2011 ◽  
Vol 19 (6) ◽  
pp. 307-316 ◽  
Author(s):  
Dina S. El-Agamy ◽  
Abdelhadi M. Shebl ◽  
Shehta A. Said
Keyword(s):  
Liver Fibrosis ◽  
Schistosoma Mansoni ◽  
Prevention And Treatment

Dynamic computed tomography with low- and high-molecular-mass contrast agents to assess microvascular permeability modifications in a model of liver fibrosis

2002 ◽  
Vol 103 (2) ◽  
pp. 213-216 ◽  
Author(s):  
Roland MATERNE ◽  
Laurence ANNET ◽  
Stéphane DECHAMBRE ◽  
Christine SEMPOUX ◽  
Anne M. SMITH ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Contrast Agents ◽  
Molecular Mass ◽  
Hepatic Fibrosis ◽  
Mean Transit Time ◽  
Distribution Volume ◽  
High Molecular Mass ◽  
Permeability Changes ◽  
Molecular Masses ◽  
The Mean

Interstitial collagen formation and transformation of the fenestrated hepatic sinusoids into continuous capillaries are major ultrastructural changes that occur in liver cirrhosis and fibrosis. These modifications lead to progressive restriction of blood–liver exchanges. The purpose of our study was to evaluate the permeability changes in a model of hepatic fibrosis by using dynamic computed tomography (CT) enhanced with contrast agents of different molecular masses. Dynamic single-section CT of the liver was performed after intravenous bolus administration of a low-molecular-mass contrast agent (iobitridol) and an experimental high-molecular-mass agent (P840) in normal control rabbits and in rabbits with hepatic fibrosis. Hepatic, aortic and portal venous time–density curves were fitted with a dual-input one-compartmental model to calculate the hepatic mean transit time and distribution volume of the contrast agents. In the rabbits with liver fibrosis, the mean transit time of the high-molecular-mass agent was shorter than that of the low-molecular-mass agent (10.0±1.8s and 12.0±1.2s respectively; P<0.05). The distribution volume accessible to the high-molecular-mass agent was also smaller (22.2±4.8% compared with 32.0±6.7%; P<0.01). In the normal rabbits, the mean transit times of the high- and low-molecular-mass agents did not differ significantly, and nor did their distribution volumes. Our results demonstrate decreased sinusoidal permeability for the high-molecular-mass agent P840 in a model of hepatic fibrosis. Non-invasive assessment of permeability changes in liver fibrosis can be performed with dynamic CT and contrast agents of different molecular masses.

scholarly journals Praziquantel in a Clay Nanoformulation Shows More Bioavailability and Higher Efficacy against Murine Schistosoma mansoni Infection

2015 ◽  
Vol 59 (6) ◽  
pp. 3501-3508 ◽  
Author(s):  
Gina S. El-Feky ◽  
Wael S. Mohamed ◽  
Hanaa E. Nasr ◽  
Naglaa M. El-Lakkany ◽  
Sayed H. Seif el-Din ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Rate Constant ◽  
Elimination Rate ◽  
New Drugs ◽  
Egg Load ◽  
Potential Cost ◽  
Time Curve ◽  
Content Type ◽  
Mmt Clay

ABSTRACTConsideration of existing compounds always simplifies and shortens the long and difficult process of discovering new drugs specifically for diseases of developing countries, an approach that may add to the significant potential cost savings. This study focused on improving the biological characteristics of the already-existing antischistosomal praziquantel (PZQ) by incorporating it into montmorillonite (MMT) clay as a delivery carrier to overcome its known bioavailability drawbacks. The oral bioavailability of a PZQ-MMT clay nanoformulation and itsin vivoefficacy againstSchistosoma mansoniwere investigated. The PZQ-MMT clay nanoformulation provided a preparation with a controlled release rate, a decrease in crystallinity, and an appreciable reduction in particle size. Uninfected and infected mice treated with PZQ-MMT clay showed 3.61- and 1.96-fold and 2.16- and 1.94-fold increases, respectively, in area under the concentration-time curve from 0 to 8 h (AUC0–8) and maximum concentration of drug in serum (Cmax), with a decrease in elimination rate constant (kel) by 2.84- and 1.35-fold and increases in the absorption rate constant (ka) and half-life (t1/2e) by 2.11- and 1.51-fold and 2.86- and 1.34-fold, respectively, versus the corresponding conventional PZQ-treated groups. This improved bioavailability has been expressed in higher efficacy of the drug, where the dose necessary to kill 50% of the worms was reduced by >3-fold (PZQ 50% effective dose [ED50] was 20.25 mg/kg of body weight for PZQ-MMT clay compared to 74.07 mg/kg for conventional PZQ), with significant reduction in total tissue egg load and increase in total immature, mature, and dead eggs in most of the drug-treated groups. This formulation showed better bioavailability, enhanced antischistosomal efficacy, and a safer profile despite the longer period of residence in the systemic circulation. Although the conventional drug's toxicity was not examined, animal mortality rates were not different between groups receiving the test PZQ-clay nanoformulation and conventional PZQ.

scholarly journals Sestrin 2 Attenuates Rat Hepatic Stellate Cell (HSC) Activation and Liver Fibrosis via an mTOR/AMPK-Dependent Mechanism

2018 ◽  
Vol 51 (5) ◽  
pp. 2111-2122 ◽  
Author(s):  
Yi-Bing Hu ◽  
Xiao-Ting Ye ◽  
Qing-Qing Zhou ◽  
Rong-Quan Fu
Keyword(s):  
Liver Fibrosis ◽  
Protein Expression ◽  
Hepatic Fibrosis ◽  
Transforming Growth Factor ◽  
Histopathological Examination ◽  
Stellate Cell ◽  
Smooth Muscle Actin ◽  
Mrna Levels ◽  
Alpha Smooth Muscle Actin

Background/Aims: Sestrin 2 is associated with the pathophysiology of several diseases. The aim of this study was to investigate the effects and potential mechanisms of Sestrin 2 in rat hepatic stellate cells (HSCs) during liver fibrogenesis. Methods: In this study, Sestrin 2 protein expression was detected in rat HSC-T6 cells challenged with transforming growth factor-β (TGF-β) and in mice treated with carbon tetrachloride (CCl4), a well-known model of hepatic fibrosis. Next, HSC-T6 cells and fibrotic mice were transfected with lentivirus. The mRNA expression levels of markers of liver fibrosis [alpha-smooth muscle actin (α-SMA) and collagen 1A1 (Col1A1)] were analyzed by quantitative reverse transcription–polymerase chain reaction (RT-PCR). Cell death and proliferation were evaluated by the MTT assay, and biochemical markers of liver damage in serum [alanine transaminase (ALT) and aspartate transaminase (AST)] were also measured using a biochemical analyzer. Histopathological examination was used to evaluate the degree of liver fibrosis, and protein expression [phospho-adenosine monophosphate-activated protein kinase (p-AMPK), AMPK, phospho-mammalian target of rapamycin (p-mTOR), and mTOR] was determined by western blotting. Results: We found that Sestrin 2 was elevated in both the HSC-T6 cell and hepatic fibrosis models. In vitro, overexpression of Sestrin 2 attenuated the mRNA levels of α-SMA and Col1A1, suppressed α-SMA protein expression, and modulated HSC-T6 cell proliferation. In vivo, overexpression of Sestrin 2 reduced the ALT and AST levels as well as the α-SMA and Col1A1 protein expression in the CCl4 model of liver fibrosis. Moreover, the degree of liver fibrosis was ameliorated. Interestingly, overexpression of Sestrin 2 increased p-AMPK but decreased p-mTOR protein expression. Conclusion: Our findings indicate that Sestrin 2 may attenuate the activation of HSCs and ameliorate liver fibrosis, most likely via upregulation of AMPK phosphorylation and suppression of the mTOR signaling pathway.

Experimental Study Oviductus ranae for the Change of α-SMA and TGF-β in Hepatic Fibrosis Rat Liver

2014 ◽  
Vol 912-914 ◽  
pp. 1940-1943
Author(s):  
Yan Li ◽  
Xiao Ou Li ◽  
Feng Hao ◽  
Lei Zhang ◽  
Lei Liu ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Fibrosis ◽  
Rat Liver ◽  
Liver Tissue ◽  
Female Rats ◽  
Control Group ◽  
Group Model ◽  
Model Group ◽  
Model Control ◽  
Oviductus Ranae

To evaluate the control effect of Oviductus ranae on liver fibrosis in rats, and the change of TGF-β and α-SMA in liver of. To explore the mechanism of Oviductus ranae decoction on liver fibrosis. Methods Wistar female rats were randomly divided into a blank control group, model control group, colchicines group, Oviductus ranae group. Using the CCl4composite approach to make the rat modle. The course of treat-mart was 12 weeks.After treatment,All the rats was killed,and the materials and blood was taken,and to detect biochemical test of liver function after eight weeks. Investigating the variation of liver histology. Meanwhile detecting protein expression of TGF-β and α-SMA and by immunehistochemical method.Result The general condition of rats in all treatment groups are worse than the blank group,but better than the model group. And the rats in the model group were all occurred in liver fibrosis,and liver fibrosis is the most serious.In a normal rat liver tissue of TGF-β and α-SMA were significantly lower in model group and each treatment group, and there were significant differences, and the TGF-β and α-SMA in expression of liver tissue in model rats of TGF-β and α-SMA the highest. Conclusion: Oviductus ranae can effectively improve liver fibrosis rats induced by CC14liver function.Oviductus ranae can reduce the expression of TGF-β1in liver tissue of hepatic fibrosis rats induced by CCl4in. This may be one of the mechanisms of Oviductus ranae in prevention and treatment of liver fibrosis. Even though both increased expression of TGF-β and α-SMA expression, is able to determine TGF-β and α-SMA for the intervention of liver TGF-β signal transduction pathway in liver fibrosis.

scholarly journals Regression of Schistosoma mansoni associated morbidity among Ugandan preschool children following praziquantel treatment: A randomised trial

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259338
Author(s):  
Allen Nalugwa ◽  
Edridah Muheki Tukahebwa ◽  
Annette Olsen ◽  
Fred Nuwaha
Keyword(s):  
Single Dose ◽  
Preschool Children ◽  
Liver Fibrosis ◽  
Schistosoma Mansoni ◽  
Randomised Trial ◽  
Double Dose ◽  
Number Of Children ◽  
Praziquantel Treatment ◽  
Significant Difference ◽  
Liver Enlargement

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

scholarly journals Association between serum and dietary antioxidant micronutrients and advanced liver fibrosis in non-alcoholic fatty liver disease: an observational study

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9838
Author(s):  
Juliana Moraes Coelho ◽  
Katia Cansanção ◽  
Renata de Mello Perez ◽  
Nathalie Carvalho Leite ◽  
Patrícia Padilha ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Dietary Intake ◽  
Hepatic Fibrosis ◽  
Fatty Liver Disease ◽  
Advanced Fibrosis ◽  
Serum Retinol ◽  
Alcoholic Fatty Liver ◽  
Advanced Liver Fibrosis ◽  
Alcoholic Fatty Liver Disease

Background Despite clinical trials with antioxidant supplementation, few studies have been conducted to evaluate the nutritional status of antioxidant vitamins and minerals, and none have reported on the status of these serum antioxidants associated with the dietary intake of antioxidants by non-alcoholic fatty liver disease (NAFLD) patients. Objective To evaluate association between serum and dietetics antioxidants with liver fibrosis in patients with NAFLD. Methods Across-section analysis with out with 72 patients diagnosed with NAFLD. Hepatic fibrosis was measured by FibroScan®, and liver stiffness ≥7.9 kPa was considered to indicate advanced fibrosis. Retinol, alpha-tocopherol, ascorbic acid, beta-carotene, serum zinc, and selenium were evaluated, as was the dietary intake of these micronutrients in the previous 24 h (using 24-h dietary recall). The Mann–Whitney test was used to compare the fibrosis groups and, a linear regression analysis was performed to determine associated risk factors between age, sex, BMI, hepatic fibrosis, and serum antioxidants. Results A high proportion of inadequate serum retinol (20.8%), vitamin C (27%), and selenium (73.6%) was observed in the patients with NAFLD, in addition to a significant inadequacy of vitamin A (98.3%) and vitamin E (100%) intake. Patients with advanced liver fibrosis had reduced levels of serum retinol (P = 0.002), with liver fibrosis being the independent risk factor associated with serum retinol lower. Conclusion Hepatic fibrosis was associated with a reduction in serum retinol and was reduced in advanced fibrosis. NAFLD patients showed an important serum deficiency and insufficient dietary intake of the evaluated micronutrients.

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