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Nitrofurazone-induced gene expressions in rat hepatocytes and their modification by N-acetylcysteine.

Authors: Ito, K  Kajikawa, S  Nii, A  Doi, K 
Citation: Ito K, etal., Exp Toxicol Pathol. 2005 Apr;56(6):333-9.
Pubmed: (View Article at PubMed) PMID:15945272
DOI: Full-text: DOI:10.1016/j.etp.2004.11.002

The antibiotic nitrofurazone (NF) at a subtoxic dose has been shown to increase hepatocyte DNA synthesis with no preceding cell damage or necrosis. This was suppressed by concomitant administration of the antioxidant N-acetylcysteine (NAC), which suggests that free radical production is involved in the process. In this study, male F344 rats were given a single oral subtoxic dose of NF to investigate the changes in genes implicated in hepatocyte proliferation between 1 and 20h postdose by real-time PCR. Some rats were also given NAC to examine the involvement of free radicals. There were transient and sequential increases in mRNA levels of c-myc and c-jun shortly after the administration, followed by tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-alpha (TGF-alpha), c-Ha-ras, and cyclin E. The increases were blocked by concomitant administration of NAC. In contrast, there were no NF-specific increases in c-fos, hepatocyte growth factor, epidermal growth factor or cyclin D1 mRNAs. These results indicate that the induction of hepatocyte proliferation by NF is triggered by free radicals, with a pathway involving increases in c-jun, c-myc, TNF-alpha, TGF-alpha, c-Ha-ras, and cyclin E. The results also indicate that NF-induced proliferation resembles that of other mitogens.

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CRRD Object Information
CRRD ID: 2289290
Created: 2008-01-28
Species: All species
Last Modified: 2008-01-28
Status: ACTIVE



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