Effect of gadolinium chloride on liver regeneration following thioacetamide-induced necrosis in rats.

Abstract

Gadolinium chloride (GD) attenuates drug-induced hepatotoxicity by selectively inactivating Kupffer cells. The effect of GD was studied in reference to postnecrotic liver regeneration induced in rats by thioacetamide (TA). Rats, intravenously pretreated with a single dose of GD (0.1 mmol/Kg), were intraperitoneally injected with TA (6.6 mmol/Kg). Hepatocytes were isolated from rats at 0, 12, 24, 48, 72 and 96 h following TA intoxication, and samples of blood and liver were obtained. Parameters related to liver damage were determined in blood. In order to evaluate the mechanisms involved in the post-necrotic regenerative state, the time course of DNA distribution and ploidy were assayed in isolated hepatocytes. The levels of circulating cytokine TNFα was assayed in serum samples. TNFα was also determined by RT-PCR in liver extracts. The results showed that GD significantly reduced the extent of necrosis. The effect of GD induced noticeable changes in the post-necrotic regeneration, causing an increased percentage of hepatocytes in S phase of the cell cycle. Hepatocytes increased their proliferation as a result of these changes. TNFα expression and serum level were diminished in rats pretreated with GD. Thus, GD pre-treatment reduced TA-induced liver injury and accelerated postnecrotic liver regeneration. No evidence of TNFα implication in this enhancement of hepatocyte proliferation and liver regeneration was found. These results demonstrate that Kupffer cells are involved in TA-induced liver damage, as well as and also in the postnecrotic proliferative liver states.

• Authors: Mirandeli Bautista, David Andres, María Cascales, José A Morales-González, María Isabel Sánchez-Reus
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 11 Issue 11 Pg. 4426-40 (Nov 04 2010) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 21151447 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Tumor Necrosis Factor-alpha
• Thioacetamide
• DNA
• Gadolinium
• gadolinium chloride

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Cell Proliferation
• DNA (metabolism)
• Gadolinium (pharmacology, therapeutic use)
• Hepatocytes (drug effects, metabolism)
• Kupffer Cells (drug effects, metabolism)
• Liver (pathology)
• Liver Regeneration (drug effects)
• Male
• Necrosis (chemically induced, drug therapy)
• Ploidies
• Rats
• Rats, Wistar
• Thioacetamide (toxicity)
• Tumor Necrosis Factor-alpha (blood, genetics, metabolism)