Chronic acetaminophen attenuates age-associated increases in cardiac ROS and apoptosis in the Fischer Brown Norway rat.
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.
Kakarla
Sunil K
SK
Department of Pharmacology, Physiology and Toxicology, Marshall University, Huntington, WV 25755, USA.
Fannin
Jacqueline C
JC
Keshavarzian
Saba
S
Katta
Anjaiah
A
Paturi
Satyanarayana
S
Nalabotu
Siva K
SK
Wu
Miaozong
M
Rice
Kevin M
KM
Manzoor
Kamran
K
Walker
Ernest M
EM
Blough
Eric R
ER
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
D018712:Analgesics, Non-Narcotic; D017382:Reactive Oxygen Species; D000082:Acetaminophen