Altered zinc homeostasis and hepatic accumulation of metallothionein in indomethacin-induced enteropathy
Sobocinski, P.Z.; Knutsen, G.L.; Canterbury, W.J.; Hauer, E.C.
Toxicology and Applied Pharmacology 50(3): 557-564
1979
ISSN/ISBN: 0041-008X PMID: 516067 Document Number: 145037
Altered Zn homeostasis is one of several metabolic sequelae of inflammation where Zn is redistributed to the liver from endogenous sources such as plasma and sequestered in hepatic metallothionein. Studies were performed on rats to determine the effect(s) of indomethacin, a potent ulcerogenic agent, on Zn metabolism. A single s.c. dose of indomethacin given to fed rats in amounts from 1-10 mg/100 g body wt produced, by 24 h, profound hypozincemia, greater intestinal absorption of Zn, induction of hepatic metallothionein synthesis and gastrointestinal lesions. These responses were significantly muted when the drug was administered to fasted rats. The effects of indomethacin on Zn homeostasis are associated with drug-induced enteropathy. Hepatic metallothionein may function, at least in part, to sequester Zn in pathophysiologic conditions.