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.

journal_name

Basic Res Cardiol

authors

Kakarla SK,Fannin JC,Keshavarzian S,Katta A,Paturi S,Nalabotu SK,Wu M,Rice KM,Manzoor K,Walker EM Jr,Blough ER

doi

10.1007/s00395-010-0094-3

subject

Has Abstract

pub_date

2010-07-01 00:00:00

pages

535-44

issue

4

eissn

0300-8428

issn

1435-1803

journal_volume

105

pub_type

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