1.Establishment of a hepatic fibrosis model induced by diethylnitrosamine in zebrafish.
Kunyuan WANG ; Li LIU ; Wencong DAI ; Xiaohui CHEN ; Xinchun ZHENG ; Jinlin HOU
Journal of Southern Medical University 2014;34(6):777-782
OBJECTIVETo establish a zebrafish model of liver fibrosis via diethylnitrosamine (DEN)-induced liver injury.
METHODSA total of 120 wild-type 3-month-old zebrafish were randomly divided into DEN-treated group and control group. The survival rate and behavioral changes of each group were observed. After treatment with DEN for 2, 4, and 6 weeks, liver index was measured, and liver fibrosis was evaluated with HE staining, Gomori staining and Sirius red staining.
RESULTSNo obvious behavioral change was observed in DEN-treated group during the experiment. Compared with that in control group, the liver index of zebrafish in DEN-treated group showed no significantly changes at the time points of observation. Proliferation of reticulate fibers was found in 30% of zebrafish treated with DEN for 4 weeks, and the rate increased to 80% at 6 weeks when reticulate fibers and collagen fibers actively proliferated to result in fiber collapse and formation of fibrotic nodules.
CONCLUSIONA stable zebrafish liver fibrosis model was successfully established by inducing liver damage to facilitate studies of the pathogenesis of liver fibrosis and screening therapeutic drugs.
Animals ; Diethylnitrosamine ; Disease Models, Animal ; Liver Cirrhosis ; chemically induced ; Zebrafish
2.The role of hepatic sinusoid capillarization during the formation of portal hypertension in fibrotic rats induced by dimethylnitrosamine.
Xiong LU ; Ping LIU ; Guang-fu XU ; Cheng-hai LIU ; Feng-hua LI ; Cheng LIU
Chinese Journal of Hepatology 2003;11(10):595-598
OBJECTIVESTo study the role of hepatic sinusoid capillarization during the formation of portal hypertension in fibrotic rats induced by dimethylnitrosamine (DMN).
METHODSHepatic fibrotic rats were induced by administration of DMN intraperitoneally three times a week for 4 weeks. The rats were harvested on day 2 and weeks 1, 2, 3, 4, 5, 6, 8, 12 and 24. The formation of liver fibrosis and hepatic sinusoid capillarization were observed by morphologic methods. Pressure of portal vein (Ppv) was directed measured with intubation tube method by mesentry anterior vein.
RESULTSThe Ppv was getting higher and higher with the administration of DMN. After four weeks, the Ppv was higher than that of control [(1.10+/-0.18)kPa vs (0.52+/-0.04)kPa, t=6.41, P<0.01]. The dynamic change of hepatic sinusoid capillarization was in accordance with that of Ppv, which normalized gradually after the DMN was stopped. Significant positive correlation existed between the dynamic change of Ppv and the expression of vWF, laminin and alpha-SMA in sinus (r=0.833, P<0.01; r=0.953, P<0.01; r=0.919, P<0.01).
CONCLUSIONHepatic sinusoid capillarization is the vital cause for portal hypertension in fibrotic rats induced by DMN.
Animals ; Capillaries ; pathology ; Dimethylnitrosamine ; Hypertension, Portal ; chemically induced ; etiology ; pathology ; Liver ; blood supply ; pathology ; Liver Cirrhosis, Experimental ; chemically induced ; complications ; pathology ; Male ; Rats ; Rats, Wistar
3.Chronic arsenic poisoning and idiopathic portal hypertension: report of a case.
Zheng WANG ; Ying JIANG ; Chong-qing YANG ; Dong-ge LIU
Chinese Journal of Pathology 2012;41(7):487-488
Adult
;
Arsenic Poisoning
;
pathology
;
Chronic Disease
;
Hemosiderin
;
metabolism
;
Hemosiderosis
;
metabolism
;
pathology
;
Humans
;
Hypertension, Portal
;
chemically induced
;
metabolism
;
pathology
;
Liver Cirrhosis
;
chemically induced
;
metabolism
;
pathology
;
Male
;
Pancytopenia
;
chemically induced
;
metabolism
;
pathology
;
Splenomegaly
;
chemically induced
;
metabolism
;
pathology
4.Liver fibrosis inhibits lethal injury through D-galactosamine/lipopolysaccharide-induced necroptosis.
Lu LI ; Li BAI ; Su Jun ZHENG ; Yu CHEN ; Zhong Ping DUAN
Chinese Journal of Hepatology 2022;30(4):413-418
Objective: To explore the new mechanism of liver fibrosis through D-galactosamine/lipopolysaccharide (D-GalN/LPS)-induced necroptosis as an entry point to inhibit lethal injury. Methods: The carbon tetrachloride (CCl4)-induced mouse model of liver fibrosis was established. At 6 weeks of fibrosis, the mice were challenged with a lethal dose of D-GalN/LPS, and the normal mice treated with the same treatment were used as the control. The experiment was divided into four groups: control group (Control), acute injury group (D-GalN/LPS), liver fibrosis group (Fib), and liver fibrosis + acute challenge group (Fib + D-GalN/LPS). Quantitative PCR and immunofluorescence were used to analyze the expression of necroptosis key signal molecules RIPK1, RIPK3, MLKL and/or P-MLKL in each group. Normal mice were treated with inhibitors targeting key signaling molecules of necroptosis, and then given an acute challenge. The inhibitory effect of D-GalN/LPS-induced-necroptosis on acute liver injury was evaluated according to the changes in transaminase levels and liver histology. Liver fibrosis spontaneous ablation model was established, and then acute challenge was given. Necroptosis key signal molecules expression was analyzed in liver tissue of mice in each group and compared by immunohistochemistry. The differences between groups were compared with t-test or analysis of variance. Results: Quantitative PCR and immunofluorescence assays result showed that D-GalN/LPS-induced significant upregulation of RIPK1, RIPK3, MLKL and/or P-MLKL. Necroptosis key signal molecules inhibition had significantly reduced D-GalN/LPS-induced liver injury, as manifested by markedly reduced serum ALT and AST levels with improvement in liver histology. Necroptosis signaling molecules expression was significantly inhibited in fibrotic livers even under acute challenge conditions. Additionally, liver fibrosis with gradual attenuation of fibrotic ablation had inhibited D-GalN/LPS-induced necroptosis. Conclusion: Liver fibrosis may protect mice from acute lethal challenge injury by inhibiting D-GalN/LPS-induced necroptosis.
Animals
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Chemical and Drug Induced Liver Injury/pathology*
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Galactosamine/adverse effects*
;
Lipopolysaccharides/adverse effects*
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Liver/pathology*
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Liver Cirrhosis/pathology*
;
Liver Failure, Acute/chemically induced*
;
Mice
;
Necroptosis
5.Acute Liver Failure Associated with Occupational Exposure to Tetrachloroethylene.
Chuan SHEN ; Cai Yan ZHAO ; Fang LIU ; Ya Dong WANG ; Wei WANG
Journal of Korean Medical Science 2011;26(1):138-142
Tetrachloroethylene is a chlorinated solvent that is primarily used in dry cleaning and degreasing operations. Although the hepatotoxicity caused by tetrachloroethylene has been well documented in literature, it is rarely considered as a cause of acute liver failure. We report a case of a 39-yr-old man who was admitted to our hospital for acute liver failure due to tetrachloroethylene exposure. Histological examination of the liver revealed massive hepatic necrosis, prominently, in zone 3 of the hepatic lobules. The patient underwent supportive treatment along with 3 sessions of plasmapheresis, and consequently, he presented a favorable outcome. Repeat liver biopsy performed 6 months after the patient's discharge showed architectural distortion with postnecrotic cirrhosis. Physicians should be aware of the possibility of acute liver failure induced by tetrachloroethylene. Early plasmapheresis can be effective for individuals with sufficient capacity for hepatocyte regeneration.
Adult
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Carcinogens/*toxicity
;
Humans
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Liver Cirrhosis/pathology
;
Liver Failure, Acute/chemically induced/*diagnosis/pathology
;
Male
;
*Occupational Exposure
;
Plasmapheresis
;
Tetrachloroethylene/*toxicity
6.Real-time elastography for quantitative assessment of liver fibrosis in a rat model.
Sen-hao LIN ; Jiao-jiao MA ; Hui ZHANG ; Hong DING ; Qing YU ; Hong-guang ZHU ; Wen-jiao ZENG ; Wen-ping WANG
Chinese Journal of Hepatology 2012;20(5):386-389
OBJECTIVETo investigate the feasibility of real-time elastography for quantitative evaluation of liver fibrosis in a rat model.
METHODSA total of 70 male Wistar rats were included in the group for dimethylnitrosamine (DMN)-induced liver injury, and 10 saline-injected rats were used as normal control. Hepatic injury was induced by a single intraperitoneal injection of DMN at a dose of 50 mg/kg of body weight. Nine or ten rats in the group with DNM injected and one or two rats in the normal control group were randomly selected and sacrificed at each of the following post-injection time: day 5, 7, 10, 14, 21, 24, and 28. And their livers were taken for pathology analysis. All the rats underwent real-time elastography before sacrificed in order to acquire area ratio of low-strain region (% AREA) and liver fibrosis index (LF index) which were compared with the stage of liver fibrosis and grade of necroinflammatory pathologically. By the different data, Spearman correlation analysis, rank-sum test or receiver operating characteristic curve was used.
RESULTSAmong 58 successfully modeled rats, there were nine, 13, 14 and 12 rats of S1, S2, S3 and S4 liver fibrosis on pathology, respectively, which were with or without mild necroinflammatory. The other 10 rats were found to be S0 with severe necroinflammatory. Values of LF index and % AREA both increased with liver fibrosis stage (P less than 0.05). There was certain correlation between LF index and liver fibrosis stage (r=0.643, P=0.000), so was % AREA and liver fibrosis stage (r=0.662, P=0.000). As for LF index, Areas under the receiver operating characteristic curve (Az) was 0.943, 0.890, 0.743 and 0.821 for the diagnosis of hepatic fibrosis S1 or higher, S2 or higher, S3 or higher and S4, respectively; as for % AREA, they were 0.948, 0.883, 0.772 and 0.842, respectively. However, we found a significant difference for LF index or % AREA between S0 with and without severe inflammatory activity rats (P=0.005 and P=0.017).
CONCLUSIONReal-time elastography is available for quantitative assessment of liver fibrosis in rats induced by DMN, but severe inflammatory activity can affect its accuracy.
Animals ; Dimethylnitrosamine ; adverse effects ; Elasticity Imaging Techniques ; Liver ; pathology ; Liver Cirrhosis, Experimental ; chemically induced ; pathology ; Male ; Rats ; Rats, Wistar
8.Amiodarone-induced Hepatitis and Polyneuropathy.
Hyun Mo KANG ; Yoon Sae KANG ; Seok Hyun KIM ; Jae Kyu SEONG ; Dae Young KANG ; Heon Young LEE ; Byung Seok LEE
The Korean Journal of Internal Medicine 2007;22(3):225-229
Amiodarone chlorhydrate is a diiodated benzofuran derivative, and it is used to treat cardiac rhythm abnormalities. Hepatotoxicity is a relatively uncommon side effect of amiodarone, and symptomatic hepatic dysfunction occurs in fewer than 1% of the patients taking amiodarone. Cirrhosis is a rare complication that's been confirmed in 12 cases. Peripheral neuropathy occurs in 10% of patients taking aminodarone. We report here on an unusual case of amiodarone-induced hepatotoxicity and peripheral neurotoxicity. A 75 year old man with normal liver function was given amiodarone for treating his atrial fibrillation and heart failure. He developed nausea, vomiting, muscle weakness and wasting after 17.8 months therapy with amiodarone (400 mg orally once per day). Liver biopsy showed the presence of foam cells in the hepatic sinusoids and Mallory bodies in the periportal hepatocytes on light microscopy. Sural nerve biopsy showed demyelination, and nerve conduction studies showed mixed sensorimotor polyneuropathy. These observations show the necessity of monitoring the hepatic function and conducting neurologic examination of the patients treated with amiodarone.
Aged
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Amiodarone/*adverse effects
;
Anti-Arrhythmia Agents/*adverse effects
;
Hepatitis, Toxic/*etiology
;
Humans
;
Liver Cirrhosis/chemically induced
;
Male
;
Polyneuropathies/*chemically induced
9.Cystic degeneration in liver injury induced by CCl4 in SD rats.
Qin XU ; Yi-ping SHEN ; An-li XU
China Journal of Chinese Materia Medica 2006;31(22):1880-1881
OBJECTIVETo explore the hepatic injury induced by CCl4in SD rat.
METHOD40 SD rats were allocated to male and female group, consisting of 20 animals/sex/group. SD rats were given at 2 mL x kg(-1) of 10% CCl4 through celiac injection per 3 day for 12 days. All rats were killed by anaesthesia of ethyl ether and bleeding through abdominal aorta at 12th day. Liver tissue was fixed in 10% neutral formalin, embedded in paraffin, cut at a nominal thickness of 3 microm, stained with hematoxylin and eosin ( H&E) , evaluated at by microscopic examination.
RESULT19 cases with local necrosis, 8 cases with fatty degeneration, 9 cases with cystic degeneration and 2 cases with fibrosis were seen in group male. 20 cases with local necrosis, 9 cases with fatty cases degeneration, 1 case with cystic degeneration and 1 case with fibrosis were seen in group female. The incidence of cystic degeneration in male group was found significantly higher than that in female group (P < 0. 05) , but the incidence of other lesions was no significant difference between male and female group.
CONCLUSIONCCl4 induces local necrosis , fatty degeneration, fibrosis and cystic degeneration in SD rat. The incidences of local necrosis , fatty degeneration and fibrosis were no significantly difference between male and female rat, but the incidence of cystic degeneration in male rats was significant higher than that in female rats.
Animals ; Carbon Tetrachloride ; Chemical and Drug Induced Liver Injury ; Cysts ; chemically induced ; pathology ; Disease Models, Animal ; Female ; Liver ; pathology ; Liver Cirrhosis ; chemically induced ; pathology ; Liver Diseases ; pathology ; Liver Neoplasms ; chemically induced ; pathology ; Male ; Precancerous Conditions ; chemically induced ; pathology ; Rats ; Rats, Sprague-Dawley ; Sex Factors
10.A comparative study of diffusion-weighted magnetic resonance imaging and pathological findings of liver fibrosis in rabbits.
Qiu-shi WANG ; Yan ZOU ; Hui LIU ; Zai-yi LIU ; Chang-hong LIANG
Journal of Southern Medical University 2009;29(10):1965-1968
OBJECTIVETo investigate the alteration of apparent diffusion coefficient (ADC) in diffusion-weighted MR imaging (MR-DWI) of liver fibrosis and its pathological basis in rabbits.
METHODSFive rabbits in the control group and 22 with experimental liver fibrosis induced by transperitoneal injection of carbon tetrachloride (CCl4) were examined with MR-DWI. Diffusion-weighted SE EPI sequence with a relatively high b factor (b=600 s/mm2) was used to measure the ADC. The mean values of ADC were compared among the rabbits in different stages of liver fibrosis and analyzed in relation to the pathological findings.
RESULTSThe mean ADC value decreased significantly with increased severity of liver fibrosis (P<0.05). Pathologically, the amount and extension of fibrotic matrix increased, and the hepatic necroinflammation worsened with the progression of the liver fibrosis.
CONCLUSIONThe ADC value decreases with the progression of liver fibrosis possibly as the result of water diffusion limitation due to increased fibrous tissue in the liver and abnormal water diffusion within the intracellular and extracellular spaces.
Animals ; Carbon Tetrachloride ; toxicity ; Liver Cirrhosis ; chemically induced ; diagnosis ; pathology ; Magnetic Resonance Imaging ; methods ; Male ; Rabbits ; Random Allocation