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Article
Acetaminophen Combinations Protect Against Iron-Induced Cardiac Damage in Gerbils
MIIR Faculty Research
  • Ernest M. Walker, Jr., Marshall University
  • Ryan G. Morrison, Marshall University
  • Lucy Dornon, Marshall University
  • Joseph P. Laurino
  • Sandra M. Walker, Marshall Community and Technical College
  • Mark Studeny, Marshall University
  • Paulette S. Wehner, Marshall University
  • Kevin M. Rice, Marshall University
  • Miaozong Wu, Marshall University
  • Eric R. Blough, Marshall University
Document Type
Article
Publication Date
10-1-2009
Abstract
This study tested if acetaminophen, N-methyl-D-glucamine dithiocarbamate (NMGDTC), deferoxamine, and combinations of these agents reduce excess iron content, prevent iron-induced pathology, reduce cardiac arrhythmias, and reduce mortality in iron-overloaded gerbils. Eight groups of 16 gerbils received iron dextran injections (ferric hydroxide dextran complex, 120 mg/kg, ip) or saline solution (controls) twice/wk for 8 wk. The 8 groups were treated every Monday, Wednesday, and Friday with one of the following: saline control, acetaminophen, 150 mg/kg, ip), acetaminophen (150 mg/kg, po), deferoxamine, 83 mg/kg, ip), NMGDTC (200 mg/kg, ip), or combinations of acetaminophen (75 mg/kg) with deferoxamine (42 mg/kg, each ip, separately) or acetaminophen (75 mg/kg) with NMGDTC (100 mg/kg, each ip, separately). The treatments were given 4 hr after each iron injection on days when both iron administration and treatment occurred during iron overloading (8 wk) and were continued 4 wk thereafter. Echocardiography (ECHO) was used to evaluate iron-induced cardiac changes and detect arrhythmias. Acetaminophen and NMGDTC, or combinations thereof, reduced cardiac and hepatic excess iron content as measured by inductively coupled plasma atomic emission spectrometry (ICP-AES). Acetaminophen was effective whether administered po or ip. Acetaminophen treatment had a positive inotropic effect on cardiac function. Acetaminophen-deferoxamine combination conferred equal cardioprotection as acetaminophen or deferoxamine alone, was equally able to remove hepatic iron, and was superior to either acetaminophen or deferoxamine in removing cardiac iron from iron-overloaded gerbils. Acetaminophen-NMGDTC combination was also effective in removing cardiac and hepatic iron and protecting against iron-induced cardiac damage. ECHO evaluation of iron-overloaded, untreated gerbils demonstrated a high incidence of cardiac arrhythmias, usually PVCs (10/16 = 63%), and mortality prior to completion of the experiment (4/16 = 25%). All treatments except deferoxamine, alone, reduced the incidence of cardiac arrhythmias and deaths. All treatments reduced iron-induced increases in hepatic and cardiac weights. This study demonstrates injection alternates that are equally or more effective than deferoxamine injections and shows oral acetaminophen to be effective in treatment of iron-overload and associated cardiac complications.
Comments

This article first appeared in the Fall 2009 issue of Annals of Clinical & Laboratory Science, the member magazine of the Association of Clinical Scientists, Inc., and is reprinted with permission.

http://www.annclinlabsci.org/content/39/4/378.full

© 2009 by the Association of Clinical Scientists, Inc.

Citation Information
Walker EM Jr., Morrison RG, Dornon L, Laurino JP, Walker SM, Studeny M, Wehner PS, Rice KM, Wu M, Blough ER (2009) Acetaminophen combinations protect against iron-induced cardiac damage in gerbils. Ann Clin Lab Sci 39:378–385.