Establishment of a Standardized Liver Fibrosis Model with Different Pathological Stages in Rats

Li, Li; Hu, Zongqiang; Li, Wen; Hu, Mei Chen; Ran, Jianghua; Chen, Peng; Sun, Qiang-Ming

doi:10.1155/2012/560345

Cited by 24 publications

(19 citation statements)

References 28 publications

(19 reference statements)

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“…The result of histopathology from this study showed that CCl 4 can induce liver injury as well as renal injury, which were consistent with the findings of previous studies [ 7 – 9 ]. Histopathology from the BSA group did not show any hepatic lesions but only renal lesions; thus we can imply that BSA overload had no apparent effect on liver histology.…”

Section: Discussionsupporting

confidence: 93%

An Attempt to Establish a Common Animal Model for Hepatorenal Fibrosis in Rats

Limbu

Liu

Cheng

et al. 2017

Pathology Research International

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It is already a proven fact that there exists a relationship between CLD (chronic liver disease) and kidney disease but still there is no available combined animal model of liver and kidney fibrosis on the same animal. An animal model is one of the important research tools in the field of medical science because it is important to build a model that can simulate the disease condition so that the particular disease can be studied. Therefore, the aim of this study is to build a less expensive, less time consuming, and reproducible model of hepatorenal fibrosis on rats. We administered combined intraperitoneal injection of CCl4 (Carbon Tetrachloride) and BSA (Bovine Serum Albumin) on a female Wistar rats. At the end, the liver and kidney tissues were examined under microscope to see whether we were successful in establishing the model or not. The results show that liver fibrosis was marked but the changes on the kidneys were mild. In this study, we were able to induce significant fibrosis in the liver and early stages of fibrosis in the kidneys. The result also demonstrated that the addition of BSA conferred a liver protective effect against CCl4 induced hepatotoxicity, whereas combination of CCl4 and BSA proved to be detrimental for kidneys.

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Section: Discussionsupporting

confidence: 93%

An Attempt to Establish a Common Animal Model for Hepatorenal Fibrosis in Rats

Limbu

Liu

Cheng

et al. 2017

Pathology Research International

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“…These models have provided support for our understanding of the mechanisms of hepatic fibrosis and have enabled us to evaluate the safety and effectiveness of novel potential therapies for liver fibrosis and cirrhosis (Ming-Ling Chang, 2005;Starkel and Leclercq, 2011;Yan Liu, 2013). Among hepatotoxins, CCl4 is often used to induce hepatic fibrosis and cirrhosis in animals because the underlying biochemical mechanisms and histological characteristics are similar to those observed in human liver cirrhosis (Constandinou et al, 2005;Fujii et al, 2010;GI-PPEUM LEE, 2005;Li et al, 2012). CYP2E1, an enzyme expressed in perivenular hepatocytes, metabolizes CCl4 into the CCl3 + radical, which causes centrilobular necrosis and alters the permeability of the plasma and mitochondrial membranes of hepatocytes (Fujii et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Establishment of a standardized mouse model of hepatic fibrosis for biomedical research

Truong¹,

Nguyen²,

Nguyen³

et al. 2014

Biomed Res Ther

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Abstract-Liver injury causes nodule and scar tissue formation and diffuse fibrosis, which are characteristic of liver cirrhosis. Since there are currently no efficacious therapies to prevent fibrosis, the development of animal models of liver fibrosis is necessary to facilitate further in vivo studies of this pathology. In this study, a mouse model of liver fibrosis was generated using Swiss mice and carbon tetrachloride (CCl 4 ) treatment. Induction of liver fibrosis was analyzed using 0.8, 1.0, or 1.2 mL/kg CCl 4 to determine the effective dose. In this study, we aimed to develop a standardized hepatic fibrosis mouse model by using CCl 4 induction to facilitate further studies in this field. In Swiss mice, we evaluated the dose of CCl 4 and the criteria of fibrosis, such as serum markers, fibrosis marker genes, and histopathology. Mice were administered CCl 4 three times per week for 8 consecutive weeks. Body weights, survival rates, levels of serum markers (aspartate aminotransferase/alanine aminotransferase [AST/ALT]) and fibrosis markers (fibronectin, procollagen, nt5e, transforming growth factor-beta [TGF-β], and integrin), and histopathology (using hematoxylin and eosin [H&E] staining) were analyzed to determine the optimal dose of CCl 4 for induction of liver fibrosis. Results showed that 1.0 mL/kg CCl 4 was the most efficient dose for the establishment of a liver fibrosis mouse model. In a standardized liver fibrosis model, mice were treated with 1.0 mL/kg CCl 4 three times per week for 11 consecutive weeks, and levels of serum markers (AST, ALT, bilirubin, and albumin), expression of fibrosis marker genes (using quantitative reverse transcription polymerase chain reaction [RT-PCR]), histopathology (using Hematoxylin and eosin staining), and connective tissue formation (using Massive trichrome staining) were analyzed. The outcomes showed that serum markers and the levels of fibrosis marker genes were significantly increased in the standardized liver fibrosis model. Additionally, we observed sharp increases in fibronectin and procollagen expression (1222.40 ± 4.20 and 241.35 ± 1.18, respectively), and the development of cirrhosis (fibrosis stage 3-5/6) in liver tissues of the standardized mouse model of hepatic fibrosis.

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“…Chronic administration of CCl 4 for 8 weeks caused liver damage characterized by an increase of ALT, AST, and ALP activity in plasma. As described by Hayashmi et al [12], Truong et al [16], and Li L et al, [18], the mechanism of CCl 4 is trichloromethyl and trichloromethyl peroxide radicals is attacked the endoplasmic reticulum membrane and leading to lipid peroxidation [12], [16], [18]. CCl 4 chronic treatments lead to impaired membrane permeability so that the enzymes in the cytosol and mitochondria of hepatocytes will come out into plasma.…”

Section: Discussionmentioning

confidence: 98%

“…ALT and AST are enzymes located in the cytosol of hepatocytes that are involved in the gluconeogenesis process. Hepatocyte injury can lead to increased activity of them up to more than 2 times normal [18]. [19], [20].…”

Section: Discussionmentioning

confidence: 99%

Antifibrotic Activity of Phaleria macrocarpa Extract in Rat Liver-fibrosis Model: Focus on Oxidative Stress Markers, TGF-β1 and MMP-13

Wardhani

Sundari

Tjandrawinata³

et al. 2020

Open Access Maced J Med Sci

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AIM: This study was aimed to determine the antifibrotic activity of Phaleria macrocarpa (PM) extract in liver fibrosis (LF) and its possible mechanism in the rat model. METHODS: Sprague Dawley male rats were injected with 2 mL/kg BW of carbon tetrachloride intraperitoneally twice a week for 2 weeks, followed by 1 mL/kg BW for 6 weeks. Afterward, the treatments began from the 3rd week: Silymarin 100 mg/kg BW/day, standardized PM extract (Proliverenol) 75 or 150 mg/kg BW/day orally. Rats were sacrificed in the 8th week. Blood and liver were collected to analyze liver function, liver damage and fibrosis marker, oxidative stress markers, pro-fibrogenic cytokine, and antifibrotic marker. RESULTS: Our study showed that the treatment of silymarin and PM resulted in the normalized activity of liver function, followed by the amelioration of oxidative stress, demonstrated by the decreased malondialdehyde levels and an increased ratio of glutathione and glutathione disulfide. All markers examined showed that PM extract has antioxidant activity due to decreased hepatic stellate cell activation. We also found a decrease in tumor growth factors-β1 and protein expressions of matrix metalloproteinases-13 in all treatment groups compared to the carbon tetrachloride group. There were tendencies of the decreased fibrotic area following improvements of biochemical parameters. CONCLUSION: PM extracts ameliorate carbon tetrachloride-induced LF. The proposed mechanism is by overcoming oxidative stress and regulating pro-fibrogenic cytokine and antifibrotic markers.

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Establishment of a Standardized Liver Fibrosis Model with Different Pathological Stages in Rats

Cited by 24 publications

References 28 publications

An Attempt to Establish a Common Animal Model for Hepatorenal Fibrosis in Rats

An Attempt to Establish a Common Animal Model for Hepatorenal Fibrosis in Rats

Establishment of a standardized mouse model of hepatic fibrosis for biomedical research

Antifibrotic Activity of Phaleria macrocarpa Extract in Rat Liver-fibrosis Model: Focus on Oxidative Stress Markers, TGF-β1 and MMP-13

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