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.