Low molecular weight heparin prevents hepatic fibrogenesis caused by carbon tetrachloride in the rat

Abe, Wataru; Ikejima, Kenichi; Lang, Tie; Okumura, Kentaro; Enomoto, Nobuyuki; Kitamura, Tsuneo; Takei, Yoshiyuki; Sato, Nobuhiro

doi:10.1016/j.jhep.2006.08.023

Cited by 105 publications

(87 citation statements)

References 45 publications

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“…Nonetheless, evidence for the role of thrombosis in liver fibrogenesis has been increasing in recent years. While possession of Factor V Leiden mutations has been shown to be a risk factor in rapid fibrosis progression in HCV [61], low-molecular weight heparin and warfarin prevented hepatic fibrogenesis caused by carbon tetrachloride in the rat [62]. Furthermore, the influence of Factor V Leiden polymorphism on fibrosis progression has been confirmed experimentally [63].…”

Section: Role Of Hepatic Sinusoids In the Pathogenesis Of Congestive mentioning

confidence: 92%

Hepatic sinusoids in liver injury, inflammation, and fibrosis: new pathophysiological insights

2016

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Section: Role Of Hepatic Sinusoids In the Pathogenesis Of Congestive mentioning

confidence: 92%

Hepatic sinusoids in liver injury, inflammation, and fibrosis: new pathophysiological insights

2016

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“…The rat model was established using the method originally described by Proctor et al [16] and since used by many others [17] , with minor modifications. Fifty male SD rats were randomLy divided into three groups: the normal control (n = 10) in which rats were not administrated CCl4 or emodin, but they were injected with olive oil and orally given sodium carboxymethylcellulose (CMC); the CCl4 group (n = 20) in which rats were subcutaneously injected with CCl4, without emodin treatment; the emodin group in which rats were injected with CCl4 and treated with emodin at 20 mg/kg.…”

Section: Establishment Of a Rat Model With Hepatic Fibrogenesis Causementioning

confidence: 99%

Emodin protects rat liver from CCl₄-induced fibrogenesis via inhibition of hepatic stellate cells activation

Dong¹,

Yan²,

Zhang³

et al. 2009

WJG

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AIM: To investigate the role of emodin in protecting the liver against fibrogenesis caused by carbon tetrachloride (CCl4) in rats and to further explore the underlying mechanisms. METHODS:Rat models of experimental hepatic fibrosis were established by injection with CCl4; the treated rats received emodin via oral administration at a dosage of 20 mg/kg twice a week at the same time. Rats injected with olive oil served as a normal group. Histopathological changes were observed by hematoxylin and eosin staining. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and hepatic hydroxyproline content were assayed by biochemical analyses. The mRNA and protein relevant to hepatic stellate cell (HSC) activation in the liver were assessed using real-time reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, western blotting and enzymelinked immunosorbent assay. RESULTS:The degree of hepatic fibrosis increased markedly in the CCl4 group compared to the normal group (P < 0.01), and decreased markedly in the emodin group compared to the CCl4 group according to METAVIR scale (P < 0.01) compared with those in the normal control group (51.02 ± 10.64 IU/L and 132.28 ± 18.14 IU/L). The activities of serum ALT and AST were significantly higher in rats injected with CCl4 (289.25 ± 68.84 IU/L and 423.89 ± 35.67 IU/L, both P < 0.05).The activities of serum ALT and AST were significantly reduced by administration of emodin (176.34 ± 4 7. 2 9 I U / L a n d 2 2 6 . 1 ± 4 4. 5 2 I U / L , b o t h P < 0.05). Compared with the normal controls (54.53 ± 13.46 mg/g), hepatic hydroxyproline content was significantly higher in rats injected with CCl4 (120.27 ± 28.47 mg/g, P < 0.05). Hepatic hydroxyproline content was significantly reduced in the rats treated with emodin at 20 mg/kg (71.25 ± 17.02 mg/g, P < 0.05).Emodin significantly protected the liver from injury by reducing serum AST and ALT activities and reducing hepatic hydroxyproline content. The mRNA levels of transforming growth factor-β1 (TGF-β1), Smad4 and α-SMA in liver tissues were significantly down-regulated in SD rats that received emodin treatment. Furthermore, significant down-regulation of serum TGF-β1 protein levels and protein expression of Smad4 and α-SMA in liver tissues was also observed in the rats. Emodin inhibited HSC activation by reducing the abundance of TGF-β1 and Smad4. CONCLUSION:Emodin protects the rat liver from CCl4-induced fibrogenesis by inhibiting HSC activation. Emodin might be a therapeutic antifibrotic agent for the treatment of hepatic fibrosis.

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“…Expression of proliferating cell nuclear antigen (PCNA) in hepatocytes was evaluated similarly by immunohistochemistry as previously described elsewhere. 13 Specimens were observed and photographed using a microscope (BH-2, Olympus Corp., Tokyo, Japan) equipped with a digital imaging system (VB-6010, Keyence Corp., Osaka, Japan).…”

Section: Animal Experiments and Operative Procedurementioning

confidence: 99%

Pioglitazone promotes survival and prevents hepatic regeneration failure after partial hepatectomy in obese and diabetic KK-Ay mice

et al. 2009

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Pathogenesis of metabolic syndrome-related nonalcoholic steatohepatitis (NASH) involves abnormal tissue-repairing responses in the liver. We investigated the effect of pioglitazone, a thiazolidinedione derivative (TZD), on hepatic regenerative responses in obese, diabetic KK-A y mice. Male KK-A y mice 9 weeks after birth underwent twothirds partial hepatectomy (PH) after repeated intragastric injections of pioglitazone (25 mg/kg) for 5 days. Almost half of the KK-A y mice died within 48 hours of PH; however, mortality was completely prevented in mice pretreated with pioglitazone. In KK-A y mice, bromodeoxyuridine (BrdU) incorporation to hepatocyte nuclei 48 hours after PH reached only 1%; however, pioglitazone pretreatment significantly increased BrdU-positive cells to 8%. Cyclin D1 was barely detectable in KK-A y mice within 48 hours after PH. In contrast, overt expression of cyclin D1 was observed 24 hours after PH in KK-A y mice pretreated with pioglitazone. Hepatic tumor necrosis factor alpha (TNF-␣) messenger RNA (mRNA) was tremendously increased 1 hour after PH in KK-A y mice, the levels reaching ninefold over C57Bl/6 given PH, whereas pioglitazone blunted this increase by almost three-fourths. Pioglitazone normalized hypoadiponectinemia in KK-A y mice almost completely. Serum interleukin (IL)-6 and leptin levels were elevated extensively 24 hours after PH in KK-A y mice, whereas the levels were largely decreased in KK-A y mice given pioglitazone. Indeed, pioglitazone prevented aberrant increases in signal transducers and activators of transcription (STAT)3 phosphorylation and suppressor of cytokine signaling (SOCS)-3 mRNA in the liver in KK-A y mice. Conclusion: These findings indicated that pioglitazone improved hepatic regeneration failure in KK-A y mice. The mechanism underlying the effect of pioglitazone on regeneration failure most likely involves normalization of expression pattern of adipokines and subsequent cytokine responses during the early stage of PH. (HEPATOLOGY 2009;

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Low molecular weight heparin prevents hepatic fibrogenesis caused by carbon tetrachloride in the rat

Cited by 105 publications

References 45 publications

Hepatic sinusoids in liver injury, inflammation, and fibrosis: new pathophysiological insights

Hepatic sinusoids in liver injury, inflammation, and fibrosis: new pathophysiological insights

Emodin protects rat liver from CCl₄-induced fibrogenesis via inhibition of hepatic stellate cells activation

Pioglitazone promotes survival and prevents hepatic regeneration failure after partial hepatectomy in obese and diabetic KK-Ay mice

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Low molecular weight heparin prevents hepatic fibrogenesis caused by carbon tetrachloride in the rat

Cited by 105 publications

References 45 publications

Hepatic sinusoids in liver injury, inflammation, and fibrosis: new pathophysiological insights

Hepatic sinusoids in liver injury, inflammation, and fibrosis: new pathophysiological insights

Emodin protects rat liver from CCl4-induced fibrogenesis via inhibition of hepatic stellate cells activation

Pioglitazone promotes survival and prevents hepatic regeneration failure after partial hepatectomy in obese and diabetic KK-Ay mice

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Emodin protects rat liver from CCl₄-induced fibrogenesis via inhibition of hepatic stellate cells activation