[Role of early growth response factor-1 signal pathway in acute intrahepatic cholestatic hepatic injury in rats].

Abstract

OBJECTIVE:

To explore the role of early growth response factor-1 (Egr-1) signal pathway in acute intrahepatic cholestatic liver injury in rats.

METHODS:

A single dose (50 mg/kg) of alpha-naphthylisothiocyanate (ANIT) was administered by gavage to each experimental rat to induce intrahepatic cholestasis. Liver tissue and serum specimens were collected from rats at 24, 48 and 72 h after the intoxication. The values of Egr-1, cytokine induced neutrophil chemoattractant 1(CINC-1), macrophage inflammatory protein-2 (MIP-2) mRNA, the protein expression of inducible nitricoxide synthase (iNOS) and the values of tumor necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6) were assayed by real-time PCR, immunohistochemistry, and ELISA, respectively. The levels of MDA, SOD, NO and MPO were assayed by thiobarbituric acid method, xanthine oxidase method, nitric acid deoxidizing assay, and colorimetric method, respectively.

RESULTS:

In the model group at 24, 48, 72 h after intoxication, the values of CINC-1 and MIP-2 mRNA were higher than those of the controls (P < 0.05). In the model group at 24, 48 h after intoxication, the value of Egr-1 mRNA was higher than that of the controls (P < 0.05), but there was no significant difference at 72 h (P < 0.05). Of the model group, the absorbance value of iNOS was lower than that of the controls at 24, 48 and 72 h (P < 0.05). Of the model group at 24, 48, 72 h after intoxication, the values of TNF alpha, IL-6, MPO and MDA were higher than those of the controls (P < 0.05), but the values of NO and SOD were lower than those of the controls (P < 0.05).

CONCLUSIONS:

Egr-1 signal pathway is involved in acute intrahepatic cholestatic liver injury induced by ANIT. After Egr-1 was activated, CINC-1 and MIP-2 are activated consequently and attract neutrophils into the liver. TNF alpha and IL-6 are activated at the same time, so neutrophils are activated and the resulting lipid peroxidation and MDA increased, injuring the liver. iNOS and NO may play a protective role in acute intrahepatic cholestatic liver injury induced by ANIT.

• Authors: Yan Ding, Lei Zhao, Zhi-hua Huang, Hong Mei, Han-ming Peng
• Journal: Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology (Zhonghua Gan Zang Bing Za Zhi) Vol. 16 Issue 3 Pg. 215-9 (Mar 2008) ISSN: 1007-3418 [Print] China
• PMID: 18364083 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CXCL1
• Chemokine CXCL2
• Cxcl1 protein, rat
• Cxcl2 protein, rat
• Early Growth Response Protein 1
• Egr1 protein, rat
• Interleukin-6
• Tumor Necrosis Factor-alpha
• 1-Naphthylisothiocyanate

Topics

• 1-Naphthylisothiocyanate
• Acute Disease
• Animals
• Chemokine CXCL1 (metabolism)
• Chemokine CXCL2 (metabolism)
• Cholestasis, Intrahepatic (chemically induced, metabolism, pathology)
• Early Growth Response Protein 1 (metabolism)
• Interleukin-6 (metabolism)
• Liver (chemistry, pathology)
• Male
• Rats
• Rats, Sprague-Dawley
• Signal Transduction
• Tumor Necrosis Factor-alpha (metabolism)