scholarly journals Protective Effect ofPhaleria macrocarpaWater Extract (Proliverenol) against Carbon Tetrachloride-Induced Liver Fibrosis in Rats: Role of TNF-αand TGF-β1

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Nanik Sundari ◽  
Vivian Soetikno ◽  
Melva Louisa ◽  
Bantari W. Wardhani ◽  
Raymond R. Tjandrawinata

Phaleria macrocarpais one of the Indonesian herbal plants which has been shown to have a hepatoprotective effect. This study was conducted to evaluate the protective effect of water extract of mahkota dewa (Phaleria macrocarpa) in liver fibrosis and to elucidate its mechanism of action. Male Sprague-Dawley rats were treated with carbon tetrachloride (CCl4) for 8 weeks to induce liver fibrosis. Rats were randomly divided into 6 groups (n=5), i.e., control group, CCl4 group, CCl4 + NAC group, CCl4 + various doses of water extract ofPhaleria macrocarpa(50, 100, and 150 mg/kg body weight). Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), liver histopathology, malondialdehyde (MDA), ratio GSH/GSSG, Tumor Necrosis Factor- (TNF-)α, and Transforming Growth Factor- (TGF-)β1were analyzed.This study demonstrated that water extract ofPhaleria macrocarpaand NAC significantly protected CCl4-induced liver injury as demonstrated by reduced AST, ALT, ALP, and fibrosis percentage compared with the CCl4-only group. In addition, water extract ofPhaleria macrocarpaand NAC significantly reduced the levels of MDA, TNF-α, and TGF-β1as well as increasing the ratio of GSH/GSSG. Water extract ofPhaleria macrocarpaprevents CCl4-induced fibrosis in rats. The prevention of liver fibrosis was at least in part through its antioxidant and anti-inflammatory activities and through its capacity to inhibit hepatic stellate cells (HSC) activation by reducing fibrogenic cytokine TGF-β1.

2020 ◽  
Author(s):  
Mengping Huang ◽  
Xin Lu ◽  
Xiaofeng Wang ◽  
Jian Shu

Abstract Background Diffusion tensor imaging (DTI) is mainly used for detecting white matter fiber in the brain. From this, DTI has been applied to assess fiber in liver disorders by prior studies. But non-sufficient data has been obtained if DTI could be used for exactly staging chronic hepatitis. This study is to assess the value of DTI for staging of liver fibrosis (F), necroinflammatory activity (A), and steatosis (S) of chronic hepatitis in rats. Methods Seventy male Sprague-Dawley rats were divided into control group(n = 10) and experimental group(n = 60). The rat models of chronic hepatitis were established by abdominal subcutaneous injections of 40% CCl4. All rats underwent 3.0T MRI. ROIs were placed on DTI to estimate MR parameters (rADC value and FA value). Histopathology was the reference standard. Multiple linear regression was used to analyze the association between MR parameters and pathology. The differences in rADC value and FA value among pathological stages were evaluated by MANOVA or ANOVA. LSD was used to test the differences between each two groups. ROC analysis was performed. Results The numbers of each pathology were as follows: F0(n = 15), F1(n = 11), F2(n = 6), F3(n = 9), F4(n = 6); A0(n = 8), A1(n = 16), A2(n = 16), A3(n = 7); S0(n = 10), S1(n = 7), S2(n = 3), S3(n = 11), S4(n = 16). The rADC value had a negative correlation with liver fibrosis (r=-0.392, P = 0.008) and inflammation (r=-0.359, P = 0.015). FA value had a positive correlation with fibrosis (r = 0.409, P = 0.005). Significant differences were found in FA value between F4 and F0 ~ F3 (P = 0.03), while no significant differences among F0 ~ F3 were found (P > 0.05). AUC of FA value in differentiating F4 from F0 ~ F3 was 0.909(p < 0.001) with 83.3% Sensitivity, 85.4% specificity when the FA value was at the cut-off of 588.089(× 10− 6mm2/s). Conclusion FA value for DTI can distinguish early cirrhosis from normal, mild and moderate liver fibrosis.


Urology ◽  
2003 ◽  
Vol 62 (2) ◽  
pp. 353-356 ◽  
Author(s):  
Feral Ozturk ◽  
Muharrem Ucar ◽  
I.Cetin Ozturk ◽  
Nigar Vardi ◽  
Kadir Batcioglu

Author(s):  
Haszianaliza Haslan ◽  
Farihah Haji Suhaimi ◽  
Srijit Das

 Objective: Consumption of Mitragyna speciosa (MS) leads to various toxicities including hepatotoxicity. Piper betle (PB) is a herb that possesses various therapeutic properties. The aim of the present study was to examine the protective effect of PB methanol extract (PBME) on MS-induced hepatotoxicity which could pave the way for any future antidote.Methods: Twenty-four male Sprague–Dawley rats were randomized into control and experimental groups. The control group was further divided into the negative (G-T80) and positive (G-PB) control groups. The G-T80 group (n=6) received oral gavage of the vehicle, 15% Tween 80. The G-PB group (n=6) received PBME 200 mg/kg/day, orally. The experimental group was divided into two groups, i.e., The G-MS and G-MS (PB) groups. The G-MS group (n=6) received only MS methanol extract (MSME) 500 mg/kg/day, while the G-MS (PB) group (n=6) received MSME with concomitant treatment with PBME.Results: Histopathology examination of the G-T80 and G-PB groups showed normal histology of the liver. The G-MS group showed liver injury features such as microvesicular steatosis, ballooning degeneration, acidophilic bodies, scattered focal necrosis, fibrous portal expansion, bridging fibrosis, sinusoidal congestion, and dilatation. These features were fewer in the G-MS (PB) group which received concomitant treatment with PBME.Conclusion: Administration of PBME exerted a protective effect against MS-induced hepatotoxicity. Future clinical trials using PB as an antidote may help in combating MS-induced hepatoxicity.


2010 ◽  
Vol 30 (10) ◽  
pp. 1584-1591 ◽  
Author(s):  
Yuan Du ◽  
Tian Wang ◽  
Na Jiang ◽  
Ru-Tong Ren ◽  
De-Lu Zhao ◽  
...  

Methyl parathion (MP) is a high venenosus insecticide. It has been used in pest control of agriculture for several years. The present study is performed to investigate the protective effect of sodium aescinate (SA) on lung injury induced by MP. Forty male Sprague-Dawley rats are randomly divided into five groups, with 8 animals in each group: control group, MP administration group, MP plus SA at doses of 0.45 mg/kg, 0.9 mg/kg and 1.8 mg/kg groups. Acetylcholinesterase (AChE) activity and nitric oxide (NO) level in plasma, myeloperoxidase (MPO) activity, NO level, and antioxidative parameters in lung tissue are assayed. Histopathological examination of lung is also performed. The results show that SA has no effect on AChE. Treatment with SA decreases the activity of MPO in lung and the level of NO in plasma and lung. The level of malondialdehyde in lung is decreased after SA treatments. SA increases the activities of superoxide dismutase, glutathione peroxidase and the content of glutathione in lung. SA administration also ameliorates lung injury induced by MP. The findings indicate that SA could protect lung injury induced by MP and the mechanism of action is related to the anti-inflammatory and anti-oxidative effect of SA.


2010 ◽  
Vol 48 (4) ◽  
pp. 1123-1128 ◽  
Author(s):  
Bae-Jin Lee ◽  
Mahinda Senevirathne ◽  
Jin-Soo Kim ◽  
Young-Mog Kim ◽  
Myung-Suk Lee ◽  
...  

2017 ◽  
Vol 37 (2) ◽  
pp. 142-154 ◽  
Author(s):  
KM Sadek ◽  
EA Saleh ◽  
SM Nasr

Background: Liver fibrosis is a noteworthy well-being issue that can prompt the progression of liver cirrhosis and hepatocellular carcinoma. Prominently, many antioxidants have been shown to have defensive impacts against liver fibrosis. Aim: Subsequently, in the present study, the viability of alpha-lipoic acid (α-LA) in ensuring against carbon tetrachloride (CCl4)-actuated liver fibrosis and the mechanism(s) involved in this defensive impact were considered in rats. Results: The present results uncovered that in the CCl4-treated group, the expression of antioxidant enzymes and matrix metalloproteinase-13 (MMP-13) messenger RNA (mRNA) was downregulated ( p < 0.05), and the levels of lipid peroxide and nitric oxide were increased ( p < 0.05) in the treated rat livers along with increased collagen deposition compared to that of the control group. Also, the gene expression levels of the proinflammatory factors interleukin-6 and tumor necrosis factor-alpha, nuclear factor-kappa B (NF-κB) p65, transforming growth factor-alpha, and inducible nitric oxide synthase (iNOS) were upregulated significantly ( p < 0.05) in the CCl4 group. These negative impacts were all restrained by α-LA. Conclusions: These outcomes show that α-LA might be compelling at forestalling collagen deposition and hepatic oxidative stress as well as downregulating the expression of hepatic proinflammatory cytokines, iNOS, and NF-κB and upregulating MMP-13 expression.


Author(s):  
Asmaa Ramadan Abdel-sttar ◽  
Marwa Mahmoud Khalaf ◽  
Amira M. Aboyoussef ◽  
Ali Ahmed Abosaif

Objective: Exposure to carbon tetrachloride leads to serious liver injury and fibrosis. This study was aimed to evaluate the hepatoprotective effects of hesperidin against carbon tetrachloride (CCl4)-induced liver fibrosis in rats compared with the reference drug silymarin. Methods: Wistar albino rats were divided into five groups, each of eight rats. Animals were allocated into a control group, corn oil group and fibrosis control group. The remaining two groups received in addition to CCl4, silymarin (100 mg/kg/d) as a reference treatment and hesperidin (200 mg/kg/d). At the end of experimental period, the biomarkers of specific fibrosis [hepatic transforming growth factor β1 (TGF-β1) and hydroxyproline (HYP)], liver function [serum alanine transaminase (ALT), aspartate transaminase (AST), albumin and total bilirubin], oxidative stress [hepatic malondialdehyde (MDA), glutathione (GSH) and catalase (CAT)], inflammatory [hepatic myeloperoxidase (MPO), serum tumor necrosis factor alpha (TNF-α)], relative liver weight, lipid profile [total cholesterol, serum triglycerides, high-density lipoprotein cholesterol (HDL-Ch) and low density lipoprotein cholesterol (LDL-Ch)] were evaluated, supported by liver histopathological study and immunohistochemistry of alpha-smooth muscle actin (α-SMA) in liver sections.Results: Hesperidin significantly decreased hepatic transforming growth factor β1, hydroxyproline, the serum liver function markers of ALT, AST and total bilirubin, the hepatic content of MDA and MPO activity, the serum pro-inflammatory cytokine TNF-α, relative liver weight, and the serum lipid profile markers cholesterol, triglycerides and LDL. On the other hand, Hesperidin significantly increased albumin, the hepatic content of GSH and CAT, and serum lipid profile of LDL. In addition, liver sections obtained from these groups showed marked histopathological and immunohistochemistry of α-SMA improvement.Conclusion: Hesperidin may be promising protective agent against liver fibrosis through improvement of liver function, modulation of the fibrous scar formation, anti-inflammatory and antioxidant potentials.


2013 ◽  
Vol 91 (12) ◽  
pp. 1055-1063 ◽  
Author(s):  
Eman Said ◽  
Shehta A. Said ◽  
Nariman M. Gameil ◽  
Elsayed M. Ammar

Sildenafil citrate is a phosphodiesterase-5 inhibitor, approved for the treatment of erectile dysfunction. It enhances nitric-oxide-induced vasodilatation and it promotes angiogenesis. A relationship between angiogenesis and hepatic fibrosis has long been speculated, where the 2 are believed to progress together. In this study, the ability of sildenafil (10 mg·(kg body mass)–1, orally, once daily) to prevent and also reverse liver fibrosis/cirrhosis experimentally induced by thioacetamide injection (200 mg·kg–1, intraperitoneal (i.p.), 3 times·week–1) in male Sprague–Dawley rats has been investigated. Sildenafil administration, either to prevent or to reverse liver fibrosis/cirrhosis significantly improved the estimated hepatic functions, reduced hepatic hydroxyproline and, in turn, hepatic collagen content, as well as reducing serum levels of the pro-fibrogenic mediator transforming growth factor β1. In co-ordination with such improvement, fibrosis grades declined and fibrosis retracted. Herein, the observed results provide evidence for the potential therapeutic efficacy of sildenafil as an antifibrotic agent.


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