In vitro assessment of paracetamol-induced toxicity in the rat Reuber hepatoma H4IIEC3/G(-) cell line competent of xenobiotics metabolism.

Abstract

H4IIEC3/G(-) cells, descendants of rat Reuber hepatoma, were characterized for their response to paracetamol (acetaminophen; AAP) toxicity during log-phase of growth. The cells in culture were found to contain high contents of constitutive and dexamethasone inducible rat cytochrome P4503A besides other CYP members reported earlier. AAP produced dose-dependent decrease in cellular growth (50% at 0.7mm). The drug steadily reduced the activity of UDP-glucuronyltransferase (UGT) towards 3-hydroxybenzo[a]pyrene, decreased the contents of UDP-glucuronic acid (UDPGA) and significantly lowered GSH contents with length of exposure. After 48hr of treatment, the GSH levels registered a fall of 50% while UGT and UDPGA exhibited a moderate decline of less than 25%. Decrease in the conjugation capacity of cells correlated with LDH leakage in the medium. Three compounds of natural origin, silymarin, kutkin and andrographolide at 10-20 mum, offered relatively modest protection ranging from 24 to 55% at best, against the growth inhibitory effect of paracetamol. The hepatoma cells investigated appeared metabolically competent to respond to AAP toxicity and might prove useful for screening of agents against AAP-induced hepatotoxicity.

• Authors: J Singh, R K Reen
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 13 Issue 6 Pg. 897-903 (Dec 1999) ISSN: 0887-2333 [Print] England
• PMID: 20654565 (Publication Type: Journal Article)