title: Chronic acetaminophen attenuates age-associated increases in cardiac ROS and apoptosis in the Fischer Brown Norway rat.
abstract: There is a growing need for pharmacological agents to manage cardiovascular disease in the rapidly growing elderly population. Here, we determine if acetaminophen is efficacious in decreasing age-related increases in cardiac reactive oxygen species (ROS) and apoptosis in aging Fischer 344 X Brown Norway rats. Compared to 6-month control animals, indices of oxidative (superoxide anion [O2( *-)] and 4-hydroxy-2-nonenal [4-HNE]) and nitrosative (protein nitrotyrosylation) stress were markedly increased in 33-month-old rat hearts. 33-month animals that had been treated with acetaminophen (30 mg/kg/day p.o. for 6 months) exhibited diminished age-related increases in cardiac ROS levels and TUNEL positive nuclei and these changes were accompanied by improvements in the Bax/Bcl2 ratio, diminished evidence of caspase-3 activation and increased phosphorylation of protein kinase B, ERK1/2, p70S6K and GSK-3beta. Taken together these results suggests that acetaminophen may attenuate the age-associated increases in the cardiomyocyte apoptosis, possibly via diminishing age associated elevation in ROS production.
authors.affiliation: Department of Pharmacology, Physiology and Toxicology, Marshall University, Huntington, WV 25755, USA.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Kakarla
authors.forename: Jacqueline C
authors.initials: JC
authors.lastname: Fannin
authors.forename: Saba
authors.initials: S
authors.lastname: Keshavarzian
authors.forename: Anjaiah
authors.initials: A
authors.lastname: Katta
authors.forename: Satyanarayana
authors.initials: S
authors.lastname: Paturi
authors.forename: Siva K
authors.initials: SK
authors.lastname: Nalabotu
authors.forename: Miaozong
authors.initials: M
authors.lastname: Wu
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Rice
authors.forename: Kamran
authors.initials: K
authors.lastname: Manzoor
authors.forename: Ernest M
authors.initials: EM
authors.lastname: Walker
authors.forename: Eric R
authors.initials: ER
authors.lastname: Blough
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018712:Analgesics, Non-Narcotic; D017382:Reactive Oxygen Species; D000082:Acetaminophen