title: Acetaminophen protects against iron-induced cardiac damage in gerbils.
abstract: There are few effective agents that safely remove excess iron from iron-overloaded individuals. Our goal was to evaluate the iron-removing effectiveness 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 ipdeferoxamine. Iron dextran was injected iptwice/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, significant reduction in left ventricular ejection fraction (-22%), and fractional shortening (-31%) during systole. Treatments with acetaminophen (ip or oral) or deferoxamine (ip) were equally effective in reducing cardiac iron content and in preventing cardiac structural and functional changes. Both agents also significantly reduced excess hepatic iron content, although acetaminophen was less effective than deferoxamine. The results suggest that acetaminophen may be useful for treatment of iron-induced pathology.
authors.affiliation: Pathology Department, Marshall University Medical School, 1542 Spring Valley Drive, Huntington, WV 25704, USA. walkere@marshall.ucla.edu
authors.forename: Ernest M
authors.initials: EM
authors.lastname: Walker
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Epling
authors.forename: Cordel
authors.initials: C
authors.lastname: Parris
authors.forename: Silvestre
authors.initials: S
authors.lastname: Cansino
authors.forename: Protip
authors.initials: P
authors.lastname: Ghosh
authors.forename: Devashish H
authors.initials: DH
authors.lastname: Desai
authors.forename: Ryan G
authors.initials: RG
authors.lastname: Morrison
authors.forename: Gary L
authors.initials: GL
authors.lastname: Wright
authors.forename: Paulette
authors.initials: P
authors.lastname: Wehner
authors.forename: Elsa I
authors.initials: EI
authors.lastname: Mangiarua
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Walker
authors.forename: Eric R
authors.initials: ER
authors.lastname: Blough
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight; D004452:Echocardiography; D005849:Gerbillinae; D006331:Heart Diseases / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D007274:Injections, Intraperitoneal; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000150:complications*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D013047:Specific Pathogen-Free Organisms; D013054:Spectrophotometry, Atomic
chemical_list: D000082:Acetaminophen; D007501:Iron