Medicine and Health Sciences Commons^™

Acetaminophen Combinations Protect Against Iron-Induced Cardiac Damage In Gerbils, Ernest M. Walker Jr., Ryan G. Morrison, Lucy Dornon, Joseph P. Laurino, Sandra M. Walker, Mark Studeny, Paulette S. Wehner, Kevin M. Rice, Miaozong Wu, Eric R. Blough

MIIR Faculty Research

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) …

Acetaminophen Prevents Aging-Associated Hyperglycemia In Aged Rats: Effect Of Aging-Associated Hyperactivation Of P38-Mapk And Erk1/2, Miaozong Wu, Devashish H. Desai, Sunil K. Kakarla, Anjaiah Katta, Satyanarayana Paturi, Anil K. Gutta, Kevin M. Rice, Ernest M. Walker Jr., Eric R. Blough

MIIR Faculty Research

Background

Aging-related hyperglycemia is associated with increased oxidative stress and diminished muscle glucose transporter-4 (Glut4) that may be regulated, at least in part, by the mitogen-activated protein kinases (MAPK).

Methods

To test the possibility that aging-related hyperglycemia can be prevented by pharmacological manipulation of MAPK hyperactivation, aged (27-month old) Fischer 344/NNiaHSD × Brown Norway/BiNia F1 (F344BN) rats were administered acetaminophen (30 mg/kg body weight/day) for 6 months in drinking water.

Results

Hepatic histopathology, serum aspartate aminotransferase and alanine aminotransferase analyses suggested that chronic acetaminophen did not cause hepatotoxicity. Compared with adult (6-month) and aged (27-month) rats, very aged rats (33-month) …

Acetaminophen Protects Against Iron-Induced Cardiac Damage In Gerbils, Ernest M. Walker Jr., Christopher P. Epling, Cordel Parris, Silvestre Cansino, Protip Ghosh, Devashish H. Desai, Ryan G. Morrison, Gary L. Wright, Paulette Wehner, Elsa I. Mangiarua, Sandra M. Walker, Eric R. Blough

MIIR Faculty Research

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 …

A Mechanistic Study Of The Protective Effects Of S-Adenosyl-L-Methionine Against Hepatotoxicity Of Acetaminophen, Marcus V. Terneus Jr.

Theses, Dissertations and Capstones

Hepatic toxicity is known to be associated with excessive doses of the over-the-counter analgesic, acetaminophen (APAP). APAP overdose is the leading cause of drug-induced liver failure in the United States. APAP hepatotoxicity is dependent on the biotransformation of APAP by cytochrome P450 to the toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI). APAP, when taken in excessive doses, can lead to severe liver damage with the potential to progress to liver failure. Despite substantial efforts in past studies, the mechanism by which APAP induces such damaging effects is not completely understood. Recent discoveries suggest that glutathione (GSH) depletion, protein alkylation and reactive metabolite …