Mechanism of Hepatoprotective Effect ofBoesenbergia rotundain Thioacetamide-Induced Liver Damage in Rats

Background. Researchers focused on developing traditional therapies as pharmacological medicines to treat liver cirrhosis.Objectives. Evaluating the hepatoprotective activity ofBoesenbergia rotunda(BR) rhizome ethanolic extract on thioacetamide-induced liver cirrhosis in rats.Methods. MaleSprague-Dawleyrats were intraperitoneally injected with 200 mg/kg TAA 3 times/week and daily oral administration of 250 mg/kg, 500 mg/kg of BR extract, and 50 mg/kg of the reference drug Silymarin for 8 weeks. At the end of the experiment, Masson’s trichrome staining was used to measure the degree of liver fibrosis. Hepatic antioxidant enzymes (CAT and GPx), nitrotyrosine, cytochrome (P450 2E1), matrix metalloproteinase (MMP-2 and MMP-9), tissue inhibitor of metalloproteinase (TIMP-1), and urinary 8-hydroxyguanosine were measured. Serum levels of transforming growth factor TGF-β1, nuclear transcription factor NF-κB, proinflammatory cytokine IL-6, and caspase-3 were evaluated. Serum protein expression and immunohistochemistry of proapoptotic Bax and antiapoptotic Bcl-2 proteins were measured and confirmed by immunohistochemistry of Bax, Bcl-2, and proliferating cell nuclear antigen (PCNA).Results. BR treatment improved liver histopathology, immunohistochemistry, and biochemistry, triggered apoptosis, and inhibited cytokines, extracellular matrix proteins, and hepatocytes proliferation.Conclusion. Liver cirrhosis progression can be inhibited by the antioxidant and anti-inflammatory activities of BR ethanolic extract while preserving the normal liver status.

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In VivoEvaluation of Ethanolic Extract ofZingiber officinaleRhizomes for Its Protective Effect against Liver Cirrhosis

BioMed Research International ◽

10.1155/2013/918460 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 18

Author(s):

Daleya Abdulaziz Bardi ◽

Mohammed Farouq Halabi ◽

Nor Azizan Abdullah ◽

Elham Rouhollahi ◽

Maryam Hajrezaie ◽

...

Keyword(s):

Liver Cirrhosis ◽

Ethanolic Extract ◽

Zingiber Officinale ◽

Hepatoprotective Activity ◽

Nuclear Antigen ◽

Sprague Dawley ◽

Group 3 ◽

Group 2 ◽

The Impact ◽

Proliferating Cell

Zingiber officinaleis a traditional medicine against various disorders including liver diseases.The aim of this study was to assess the hepatoprotective activity of the ethanolic extract of rhizomes ofZ. officinale(ERZO) against thioacetamide-induced hepatotoxicity in rats. Five groups of maleSprague Dawleyhave been used. In group 1 rats received intraperitoneal (i.p.) injection of normal saline while groups 2–5 received thioacetamide (TAA, 200 mg/kg; i.p.) for induction of liver cirrhosis, thrice weekly for eight weeks. Group 3 received 50 mg/kg of silymarin. The rats in groups 4 and 5 received 250 and 500 mg/kg of ERZO (dissolved in 10% Tween), respectively. Hepatic damage was assessed grossly and microscopically for all of the groups. Results confirmed the induction of liver cirrhosis in group 2 whilst administration of silymarin or ERZO significantly reduced the impact of thioacetamide toxicity. These groups decreased fibrosis of the liver tissues. Immunohistochemistry assessment against proliferating cell nuclear antigen did not show remarkable proliferation in the ERZO-treated rats when compared with group 2. Moreover, factions of the ERZO extract were tested on Hep-G2 cells and showed antiproliferative activity (IC5038–60 μg/mL). This study showed hepatoprotective effect of ERZO.

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PASS-Predicted Hepatoprotective Activity ofCaesalpinia sappanin Thioacetamide-Induced Liver Fibrosis in Rats

The Scientific World JOURNAL ◽

10.1155/2014/301879 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12 ◽

Cited By ~ 16

Author(s):

Farkaad A. Kadir ◽

Normadiah M. Kassim ◽

Mahmood Ameen Abdulla ◽

Behnam Kamalidehghan ◽

Fatemeh Ahmadipour ◽

...

Keyword(s):

Liver Fibrosis ◽

Transforming Growth Factor ◽

Antioxidant Activities ◽

Smooth Muscle Actin ◽

Immunohistochemical Analysis ◽

Hepatoprotective Activity ◽

Nuclear Antigen ◽

Sprague Dawley ◽

Liver Fibrogenesis

The antifibrotic effects of traditional medicinal herbCaesalpinia sappan(CS) extract on liver fibrosis induced by thioacetamide (TAA) and the expression of transforming growth factorβ1 (TGF-β1),α-smooth muscle actin (αSMA), and proliferating cell nuclear antigen (PCNA) in rats were studied. A computer-aided prediction of antioxidant and hepatoprotective activities was primarily performed with the Prediction Activity Spectra of the Substance (PASS) Program. Liver fibrosis was induced in male Sprague Dawley rats by TAA administration (0.03% w/v) in drinking water for a period of 12 weeks. Rats were divided into seven groups: control, TAA, Silymarin (SY), and CS 300 mg/kg body weight and 100 mg/kg groups. The effect of CS on liver fibrogenesis was determined by Masson’s trichrome staining, immunohistochemical analysis, and western blotting.In vivodetermination of hepatic antioxidant activities, cytochrome P450 2E1 (CYP2E1), and matrix metalloproteinases (MPPS) was employed. CS treatment had significantly increased hepatic antioxidant enzymes activity in the TAA-treated rats. Liver fibrosis was greatly alleviated in rats when treated with CS extract. CS treatment was noted to normalize the expression of TGF-β1,αSMA, PCNA, MMPs, and TIMP1 proteins. PASS-predicted plant activity could efficiently guide in selecting a promising pharmaceutical lead with high accuracy and required antioxidant and hepatoprotective properties.

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Adipokine Chemerin Stimulates Progression of Atherosclerosis in ApoE−/− Mice

BioMed Research International ◽

10.1155/2019/7157865 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Huadong Liu ◽

Wei Xiong ◽

Yu Luo ◽

Hua Chen ◽

Yaqiong He ◽

...

Keyword(s):

P38 Mapk ◽

High Fat Diet ◽

Transforming Growth Factor ◽

Elevated Serum ◽

Serum Levels ◽

Nuclear Antigen ◽

High Fat ◽

Aortic Plaque ◽

Protein Levels ◽

Progression Of Atherosclerosis

Background. Vascular remodeling is the most critical pathogenesis of atherosclerosis. Adipokine chemerin was known for its relationship with obesity as well as metabolism. Most recently, chemerin was found to play a crucial role in the pathologic process of cardiovascular diseases including coronary heart disease. In this study, we surveyed the role of chemerin in progression of atherosclerosis in ApoE−/− mice. Objective. To investigate the relationship between chemerin and progression of atherosclerosis in ApoE−/− mice and its mechanism. Methods. 8-week-old ApoE−/− mice were fed with high-fat diet to induce the atherosclerosis model. Adenoviruses were transfected for knockdown or overexpression of chemerin gene into aorta. Serums and aortic tissues of ApoE−/− mice were obtained after feeding high-fat diet for 16 weeks. HE staining and oil red staining were performed to evaluate aortic plaque. ELISA was performed to explore serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and transforming growth factor-β1 (TGF-β1). Real-time PCR and western blotting were carried out to investigate the mRNA and protein levels of chemerin, nuclear factor-κB p65 (NF-κBp65), proliferating cell nuclear antigen (PCNA), phosphorylated p38 mitogen-activated protein kinase (p-p38-MAPK), phosphorylated c-Jun N-terminal kinase (p-JNK), and phosphorylated extracellular signal regulated kinase 1/2 (p-ERK 1/2). Result. Aortic plaque formation was significantly induced by high-fat diet in ApoE−/− mice. Simultaneously, elevated serum levels of TNF-α and IL-1β and elevated mRNA and protein levels of chemerin, NF-κBp65, PCNA, p-p38-MAPK, p-JNK, and p-ERK 1/2 were found in ApoE−/− mice. After aortic chemerin gene was inhibited by adenovirus, aortic atherosclerosis induced by high-fat diet was significantly meliorated, serum levels of TNF-α and IL-1β decreased, mRNA and protein levels of NF-κBp65, PCNA, p-p38-MAPK, p-JNK, and p-ERK 1/2 decreased simultaneously. Conclusion. Our study revealed that chemerin stimulated the progression of atherosclerosis in ApoE−/− mice.

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Antioxidant and Hepatoprotective Activity of a New Tablets Formulation fromTamarindus indicaL.

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/3918219 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 7

Author(s):

Jesús Rafael Rodriguez Amado ◽

Ariadna Lafourcade Prada ◽

Julio Cesar Escalona Arranz ◽

Renato Pérez Rosés ◽

Humberto Morris Quevedo ◽

...

Keyword(s):

Lipid Peroxidation ◽

Serum Levels ◽

Hepatoprotective Activity ◽

Negative Control ◽

Diet Group ◽

Control Group ◽

Standard Diet ◽

Tamarindus Indica ◽

Sprague Dawley ◽

Group I

Hepatotoxic chemicals damage liver cells primarily by producing reactive oxygen species. The decoction of the leaves ofTamarindus indicaL. is used for liver disorders. In this work we evaluated the hepatoprotective activity of a tablet formulation of this plant. Thirty-five Sprague Dawley rats were randomly divided into five groups (n=7). First group (I) is control group, fed with standard diet. Groups II to V (hepatotoxic groups) were subjected to a subcutaneous injection of CCl4(0.5 mL/kg). Group II was negative control, fed with standard diet; group III was subjected to administration of Silymarin 150 mg/kg and groups IV and V were treated with tablets in dose of 100 mg/kg and 200 mg/kg, respectively. Lipid peroxidation and the activity of superoxide dismutase, catalase, and reduced glutathione were evaluated. Serum levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamine transferase, alkaline phosphatase, and a lipid profile were evaluated too. The tablets inhibit lipid peroxidation. The redox balance (SOD-CAT-GSH) remains normal in the experimental groups treated with tablets. The liver function using dose of 200 mg/kg of tablets was better than the other experimental groups. These results justify, scientifically, the ethnobotanical use of the leaves ofTamarindus indicaL.

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Effects of Siniruangan Recipe on Proliferation, Apoptosis and Activation of Human Hepatic Stellate Cell Line LX-2

Pharmacology ◽

10.1159/000500800 ◽

2019 ◽

Vol 104 (5-6) ◽

pp. 342-351 ◽

Cited By ~ 1

Author(s):

Jinming Liu ◽

Guorong Zhao ◽

Bichen Ai ◽

Yirong He ◽

Ming Mei ◽

...

Keyword(s):

Liver Cirrhosis ◽

Liver Fibrosis ◽

Cell Apoptosis ◽

Transforming Growth Factor ◽

Stellate Cell ◽

Cell Activity ◽

Relative Content ◽

Tissue Inhibitor Of Metalloproteinase ◽

Cell Counting ◽

Tgf Β1

Background: Experimental and clinical evidence suggests that liver fibrosis is potentially reversible. Hepatic stellate cells (HSCs) play a key role in the development of hepatic fibrosis. Previous clinical applications and researches showed that Siniruangan recipe (SNRG) reversed liver fibrosis and even liver cirrhosis. This experimental study aimed to elucidate the effects of SNRG on the proliferation, apoptosis and activation of HSCs. Methods: The human HSCs line LX-2 was cultured with normal culture medium and multi-dose SNRG water decoction for 48 h. Cell Counting Kit-8 assay was used to detect the proliferation and cytotoxicity of LX-2 cells. Annexin V-FITC/PI double staining was performed to identify apoptotic cells. Immunofluorescence staining was used to determine the relative content of cleaved caspase-3, tissue inhibitor of metalloproteinase-1 (TIMP-1) and transforming growth factor-β1 (TGF-β1) in LX-2 cells. Western blot was used to detect the relative content of Bcl-2, Bax, α-smooth muscle actin, β-catenin and TIMP-1 protein expression in LX-2 cells. Results: The SNRG inhibited the proliferation of LX-2 and induced cell apoptosis through caspase-dependent and mitochondrial-dependent pathways. SNRG may inhibit the activation of LX-2 through the β-catenin pathway. The decrease in TIMP-1 and TGF-β1 protein induced by SNRG promoted the degradation of the extracellular matrix (ECM). Conclusions: SNRG induced LX-2 cell apoptosis, inhibited cell proliferation, decreased LX-2 cell activity and promoted the degradation of ECM in vitro, which may be important mechanisms for reversing liver fibrosis and liver cirrhosis.

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SMAD3 regulates the diverse functions of rat granulosa cells relating to the FSHR/PKA signaling pathway

Reproduction ◽

10.1530/rep-12-0325 ◽

2013 ◽

Vol 146 (2) ◽

pp. 169-179 ◽

Cited By ~ 15

Author(s):

Yexia Li ◽

Yujie Jin ◽

Yuxia Liu ◽

Chunyan Shen ◽

Jingxia Dong ◽

...

Keyword(s):

Granulosa Cells ◽

Transforming Growth Factor ◽

Ovarian Follicle ◽

Transforming Growth Factor Β ◽

Female Rats ◽

Nuclear Antigen ◽

Follicle Development ◽

Sprague Dawley ◽

Ovarian Follicle Development ◽

Estrogen Production

The function of Smad3, a downstream signaling protein of the transforming growth factor β (TGFβ) pathway, in ovarian follicle development remains to be elucidated. The effects of Smad3 on ovarian granulosa cells (GCs) in rat were studied. Female rats (21 days of age Sprague–Dawley) received i.p. injections of pregnant mare serum gonadotropin, and GCs were harvested for primary culture 48 h later. These cells were engineered to overexpress or knockdown Smad3, which were validated by immunohistochemistry and western blot. The expression of proliferating cell nuclear antigen (PCNA), cyclin D2, TGFβ receptor II (TGFβRII), protein kinase A (PKA), and FSH receptor (FSHR) was also detected by western blotting. Cell cycle and apoptosis of GCs were assayed by flow cytometry. The level of estrogen secreted by GCs was detected by ELISA. Smad3 overexpression promoted estrogen production and proliferation while inhibiting apoptosis of GCs. Reduction in Smad3 by RNAi resulted in reduced estrogen production and proliferation and increased apoptosis of GCs. Manipulation of Smad3 expression also resulted in changes in FSHR and PKA expression, suggesting that the effects of Smad3 on follicle development are related to FSHR-mediated cAMP signaling.

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Mitochondria-targeted antioxidant mitoquinone attenuates liver inflammation and fibrosis in cirrhotic rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00135.2019 ◽

2020 ◽

Vol 318 (2) ◽

pp. G298-G304 ◽

Cited By ~ 5

Author(s):

Saadet Turkseven ◽

Massimo Bolognesi ◽

Alessandra Brocca ◽

Paola Pesce ◽

Paolo Angeli ◽

...

Keyword(s):

Oxidative Stress ◽

Superoxide Dismutase ◽

Liver Cirrhosis ◽

Transforming Growth Factor ◽

Resistance Index ◽

Tissue Inhibitor Of Metalloproteinase ◽

Liver Inflammation ◽

Hepatic Oxidative Stress ◽

Duct Ligation ◽

Tnf Α

In liver cirrhosis, oxidative stress plays a major role in promoting liver inflammation and fibrosis. Mitochondria dysregulation is responsible for excessive reactive oxygen species production. Therefore, in an experimental model of cirrhosis, we investigated the effect of mitochondria-targeted antioxidant mitoquinone. Liver cirrhosis was induced in Spraque-Dawley rats by common bile duct ligation (CBDL). Mitoquinone (10 mg·kg−1·day−1, oral gavage) or vehicle was administered from 3rd to 28th day after CBDL, when animals were euthanized; liver oxidative stress, inflammation, fibrosis, mitophagy were evaluated; and in vivo and ex vivo hemodynamic studies were performed. In cirrhotic rats, mitoquinone prevented liver inflammation, hepatocyte necrosis, and fibrosis at histological examination; decreased circulating TNF-α, gene expression of transforming growth factor-β1, collagen type 1a1, TNF-α, IL-6, IL-1β, tissue inhibitor of metalloproteinase-1, matrix metalloproteinase (MMP)-2, and MMP-13; and reduced hepatic oxidative stress, as shown by reduced oxidative carbonylation of the proteins, by modulating antioxidants catalase, Mn superoxide dismutase, and Cu/Zn superoxide dismutase. Furthermore, mitoquinone attenuated apoptosis by reducing hepatic protein expression of cleaved caspase-3. A selective removal of dysfunctional mitochondria was improved by mitoquinone, as shown by the increase in Parkin translocation to mitochondria. Treatment with mitoquinone normalized the weight of the spleen; however, it increased portal blood flow and reduced splenic artery intrahepatic resistance, suggesting an effect on resistance index. Mitochondria-targeted antioxidant mitoquinone improves liver inflammation and fibrosis in cirrhotic rats by reducing hepatic oxidative stress, preventing apoptosis, and promoting removal of dysfunctional mitochondria. Therefore, it may represent a promising strategy for the prevention and treatment of liver cirrhosis.

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Hepatoprotective Effect of the Fruits of Polygonum orientale L. Against Carbon Tetrachloride-Induced Liver Fibrosis in Mice

Natural Product Communications ◽

10.1177/1934578x20971501 ◽

2020 ◽

Vol 15 (11) ◽

pp. 1934578X2097150

Author(s):

Yung-Jia Chiu ◽

Kun-Chang Wu ◽

Jen-Chieh Tsai ◽

Chun-Pin Kao ◽

Jung Chao ◽

...

Keyword(s):

Carbon Tetrachloride ◽

Growth Factor ◽

Liver Injury ◽

Transforming Growth Factor ◽

Smooth Muscle Actin ◽

Transforming Growth Factor Β ◽

Serum Levels ◽

Hepatoprotective Activity ◽

Tissue Growth ◽

Factor Α

The aim of this study was to evaluate the hepatoprotective effects of the fruits of Polygonum orientale L. (POE) against fibrosis in carbon tetrachloride (CCl4)-induced liver injury. Bioactive components of POE were identified using liquid chromatography (LC)-mass spectrometry (MS)/MS by comparison with standards. Treatment with either silymarin (200 mg/kg) or POE (0.5 and 1.0 g/kg) caused significant decreases in the serum levels of enzymes and reduced the extent of liver lesions and fibrosis in histological analysis. POE (0.5 and 1.0 g/kg) decreased the levels of malondialdehyde, nitric oxide, proinflammatory cytokines (ie, tumor necrosis factor-α, interleukin [IL]-1β, and IL-6), an inflammatory cytokine (ie, cyclooxygenase-2), a profibrotic cytokine (ie, transforming growth factor-β), and fibrosis-related proteins (ie, connective tissue growth factor and α-smooth muscle actin) in the liver and enhanced the activities of the antioxidative enzymes superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase. Quantitative analysis of the active constituents in POE revealed an extract composition of 3.4 mg/g of protocatechuic acid, 20.8 mg/g of taxifolin, and 5.6 mg/g of quercetin. We have demonstrated that the hepatoprotective mechanisms of POE are likely to be associated with the decrease in inflammatory cytokines by increasing the activities of antioxidant enzymes. Our findings provide evidence that POE possesses a hepatoprotective activity to ameliorate chronic liver injury.

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Evaluation of Hepatoprotective activity of Ethanolic Extract of Garuga pinnata Roxburgh leaves against Carbon tetrachloride induced Hepatotoxicity in rats.

Research Journal of Pharmacy and Technology ◽

10.52711/0974-360x.2021.00419 ◽

2021 ◽

pp. 2375-2380

Author(s):

Sandeep Chavan ◽

Remeth Dias ◽

Chandrakant Magdum

Keyword(s):

Carbon Tetrachloride ◽

Biochemical Parameters ◽

Histopathological Examination ◽

Liquid Paraffin ◽

Ethanolic Extract ◽

Serum Levels ◽

Hepatoprotective Activity ◽

Antioxidant Defense Enzymes ◽

Serum Glutamate

In this study we investigated the in vivo Hepatoprotective activity of ethanolic extract of Garuga pinnata (EEGP) leaves in Carbon tetrachloride (CCl4) induced hepatotoxicity using wistar rats of either sex as model. Hepatotoxicity was induced by the administration of CCl4 intraperitoneally (0.125ml CCl4 in liquid paraffin (1:1) per 100g body weight). Garuga pinnata leaves extract at different dose levels (200 and 400mg/kg, p.o.) showed the dose dependant hepatoprotective effect and was compared with well known standard hepatoprotective Silymarain (100mg/kg). When groups were treated with CCl4, significant increase in serum biochemical parameters such as Serum Glutamate Oxaloacetate Transaminase (SGOT), Serum Glutamate Pyruvate Transaminase (SGPT), Alkaline phosphate (ALP), Acid Phosphate (ACP), Creatinine and alteration of tissue biochemical parameters such as reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (LPO), and the total proteins were observed. The histopathological examination of the CCl4 treated groups showed sinusoidal congestion, centrilobular necrosis, marked vacuolations and congestion. However, pretreatment with extract of leaves of Garuga pinnata significantly reduced the increased serum levels of biochemical parameters and restored antioxidant defense enzymes level to its normal. Moreover, histopathology of leaves extract treated groups showed normal architecture with minimal sinusoidal congestion. Taken together, our study concludes that EEGP to be a more potential agent for caring liver from CCl4 induced damage.

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Hepatoprotective activity of Tamarindus indica Linn stem bark ethanolic extract against hepatic damage induced by co-administration of antitubercular drugs isoniazid and rifampicin in Sprague Dawley rats

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2017-0173 ◽

2018 ◽

Vol 30 (1) ◽

pp. 131-137 ◽

Cited By ~ 1

Author(s):

Shaikh Zohra Meena ◽

Md. Azizur Rahman ◽

Paramdeep Bagga ◽

Md. Mujahid

Keyword(s):

Ethanolic Extract ◽

Stem Bark ◽

Hepatoprotective Activity ◽

Group Iv ◽

Hepatic Damage ◽

Sprague Dawley ◽

Group V ◽

Group Iii ◽

Group I ◽

Sprague Dawley Rats

Abstract Background Development of drug-induced hepatic damage (DIHD) during chemotherapy is the most common reason for interruption in chemotherapy. This study evaluated the hepatoprotective activity of the ethanolic extract of Tamarindus indica stem bark (EETI) against the induced DIHD in Sprague Dawley rats. Methods The rats were divided into five groups (n=5). Group I, group III, group IV, and group V rats received 1 mL 1% carboxymethyl cellulose, EETI 100 mg/kg body weight (b.wt), EETI 200 mg/kg b.wt, and silymarin 100 mg/kg b.wt, respectively, orally once every day for 28 days. After 1 h–group II, group III, group IV, and group V rats were administered with isoniazid (INH) and rifampicin (RIF) 50 mg/kg b.wt each orally once every day for 28 days. Then, 24 h after the last dosing, blood was withdrawn from the rats and analyzed for liver specific enzymes and biochemical markers. They were examined for histopathology. Results Co-administration of INH and RIF in group II significantly increased alanine transaminase, aspartate transaminase, alkaline phosphatase, lactate dehydrogenase, serum bilirubin, and cholesterol levels while reduced the total protein and albumin levels compared to that of group I. EETI in group III and group IV rats significantly restored the liver specific enzymes and biochemical markers altered due to co-administration of INH and RIF to normal in a dose-dependent manner. EETI 200 mg/kg b.wt showed better protection to liver than EETI 100 mg/kg b.wt and was comparable to silymarin 100 mg/kg b.wt. It was well supported with histopathology of liver tissues. Conclusions EETI possesses hepatoprotective activity against DIHD in rats. It may have a substantial impact on developing clinical strategies to treat patients with hepatic damage.

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