Liver resistance to toxic effects of CCl4 under conditions of gadolinium chloride depression of Kupffer cells

Cyrendorzhiev, D. D.; Kutina, S. N.; Zubakhin, A. A.

doi:10.1007/bf02434890

Cited by 2 publications

(1 citation statement)

References 7 publications

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“…In support of this hypothesis, liver injury is potentiated and repair is attenuated after acute CCl 4 exposure in mice depleted of Kupffer cells, the resident macrophage in the liver, as well as in mice deficient in the MCP-1 receptor, CCR2. 44,45 Together, these data indicate that recruitment of macrophages is an integral component to wound healing in the liver after CCl 4 exposure and that Egr-1 deficiency impairs this response.…”

Section: Discussionmentioning

confidence: 83%

Hepatic Fibrosis Is Enhanced and Accompanied by Robust Oval Cell Activation after Chronic Carbon Tetrachloride Administration to Egr-1-Deficient Mice

Pritchard

Nagy

2010

The American Journal of Pathology

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The transcription factor early growth response (Egr)؊1 regulates the expression of genes required for execution of the wound healing response. Multiple cycles of injury, coupled to incomplete wound healing, lead to fibrosis. Therefore, we hypothesized that Egr-1 is required for the development of hepatic fibrosis. To test this hypothesis, we exposed wildtype and egr-1 ؊/؊ mice to acute or chronic carbon tetrachloride (CCl 4 ). Acute CCl 4 exposure established a profibrotic milieu in the liver, including activation of hepatic stellate cells as well as expression of type 1 collagen genes and tissue inhibitor of matrix metalloproteinase 1 in both wild-type and egr-1 ؊/؊ mice. This response was exacerbated in egr-1 ؊/؊ mice. After chronic CCl 4 exposure, hepatic fibrosis was established in both genotypes; however, the fibrotic response was profoundly worsened in Egr-1-deficient mice. Importantly, enhanced fibrosis in egr-1 ؊/؊ mice was accompanied by a robust activation of the oval cell response, suggesting more severe liver injury and/or reduced hepatocyte proliferation when compared with wild-type mice. Hepatic expression of genes indicative of oval cell activation, as well as the number of cells expressing A6, a mouse oval cell marker, was greater in egr-1 ؊/؊ mice. Taken together, these data reveal novel roles for Egr-1 as a negative regulator of both CCl 4 -induced hepatic fibrosis and the oval cell response.

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Section: Discussionmentioning

confidence: 83%

Hepatic Fibrosis Is Enhanced and Accompanied by Robust Oval Cell Activation after Chronic Carbon Tetrachloride Administration to Egr-1-Deficient Mice

Pritchard

Nagy

2010

The American Journal of Pathology

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Lead nitrate and gadolinium chloride administration modify hepatocyte cell surfaces

Pagliara

Chionna²,

Carlà³

et al. 2003

Cell Tissue Res

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Modifications of hepatocyte cell surface were determined after single i.v. injection to rats of Pb(NO 3 ) 2 (known to induce liver hyperplasia followed by apoptosis) or GdCl 3 (known to induce proliferation of parenchymal cells and Kupffer cell depletion) or administration of GdCl 3 24 h before Pb(NO 3 ) 2 injection (known to reduce hyperplasia and apoptosis induced in the parenchymal liver cells by the single Pb(NO 3 ) 2 injection). Rats were sacrificed at fixed times after the treatments (1, 3 and 5 days) and hepatocytes were isolated by enzymatic liver perfusion. In spite of the intracellular target of the heavy metals, signals leading to liver hyperplasia and apoptosis (with rates different for the different experimental conditions) were generated, which in turn were responsible for cell surface alteration. Increment or decrement of phosphatidylserine (PS) expression, asialoglycoprotein receptors (ASGPRs) and sugar residue expression on hepatocyte surfaces was measured in parallel with apoptosis and proliferation. When GdCl 3 was injected 24 h before Pb(NO 3 ) 2 injection, liver modifications were significantly reduced, thus suggesting that GdCl 3 could prevent and/or reduce liver damage.

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Liver resistance to toxic effects of CCl4 under conditions of gadolinium chloride depression of Kupffer cells

Cited by 2 publications

References 7 publications

Hepatic Fibrosis Is Enhanced and Accompanied by Robust Oval Cell Activation after Chronic Carbon Tetrachloride Administration to Egr-1-Deficient Mice

Hepatic Fibrosis Is Enhanced and Accompanied by Robust Oval Cell Activation after Chronic Carbon Tetrachloride Administration to Egr-1-Deficient Mice

Lead nitrate and gadolinium chloride administration modify hepatocyte cell surfaces

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