Acetaminophen Protects Against Iron-Induced Cardiac Damage in Gerbils

Th ere are few eff ective agents that safely remove excess iron from iron-overloaded individuals. Our goal was to evaluate the iron-removing eff ectiveness of acetaminophen given ip or orally in the gerbil iron-overload model. Male gerbils were divided into 5 groups: saline controls, iron-overloaded controls, iron-overloaded treated with ip acetaminophen, iron-overloaded treated with oral acetaminophen, and iron-overloaded treated with ip deferoxamine. Iron dextran was injected ip twice/wk for 8 wk. Acetaminophen and deferoxamine treatments were given on Mondays, Wednesdays, and Fridays during the same 8 wk and continued for 4 wk after completion of iron-overloading. Echocardiograms were performed after completion of the iron-overloading and drug treatments. Liver and cardiac iron contents were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES). Iron-overloaded controls had 232-fold and 16- fold increases in liver and cardiac iron content, respectively, compared to saline controls. In iron-overloaded controls, echocardiography showed cardiac hypertrophy, right and left ventricular distension, signifi cant reduction in left ventricular ejection fraction (-22%), and fractional shortening (-31%) during systole. Treatments with acetaminophen (ip or oral) or deferoxamine (ip) were equally eff ective in reducing cardiac iron content and in preventing cardiac structural and functional changes. Both agents also signifi cantly reduced excess hepatic iron content, although acetaminophen was less eff ective than deferoxamine. Th e results suggest that acetaminophen may be useful for treatment of iron-induced pathology.