Late administration of COX-2 inhibitors minimize hepatic necrosis in chloroform induced liver injury

Carmen K. Begay, A. Jay Gandolfi

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Our previous studies have described the protective effects of hepatoprotective agents against liver injury elicited by chloroform even when given 24 h after the toxicant, at a time when the liver injury is taking place and rapidly developing. However, the mechanisms involved in this protection remain unknown. The cytoprotective mechanism of these hepatoprotectants such as DMSO, may be due to a dramatic shift in the production of prostaglandins that are responsible for controlling the degree of inflammatory response that can affect blood flow in the liver. In this study, NS-398, a specific COX-2 inhibitor, and indomethacin, a COX-1 and COX-2 inhibitor, were administered 24 h after chloroform dosing to determine their effect on liver injury in Sprague-Dawley rats. The extent of necrosis was evaluated by H&E staining, while injury to hepatocytes was evaluated by measuring plasma levels of alanine transaminase (ALT). Both COX inhibitors, indomethacin and NS-398, prevented an increase in (ALT) at 48 h after initial toxicant insult and attenuated further liver necrosis. No changes in cellular proliferative activity occurred in all the treatment groups, which indicates that protection from the Cyclooxygenase (COX) inhibitors did not have an effect on regeneration of cells at 32 and 48 h. These results indicate COX inhibitors provide a significant protective effect on liver cells against CHCl3 injury and may provide further insight into therapeutic interventions against hepatotoxicants.

Original languageEnglish (US)
Pages (from-to)79-87
Number of pages9
JournalToxicology
Volume185
Issue number1-2
DOIs
StatePublished - Mar 14 2003

Keywords

  • Chloroform
  • Cyclooxygenase-1
  • Cyclooxygenase-2
  • Hepatotoxicity
  • Sprague-Dawley rats

ASJC Scopus subject areas

  • Toxicology

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