The Effects of Aging on Indices of Oxidative Stress and Apoptosis in the Female Fischer 344/Nnia X Brown Norway/BiNia Rat Heart

Jacqueline Fannin1, 4, Kevin M. Rice3, 4, ^, Srininvas Thulluri4, Ravi Kumar Arvapalli4, Paulette Wehner2, Eric R. Blough*, 1, 4, 5
1 Department of Pharmacology, Physiology, and Toxicology, Joan C. Edwards School of Medicine, Marshall University, USA
2 Department of Cardiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA
3 Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington WV, USA
4 Center for Diagnostic Nanosystems, Marshall University, Huntington WV, USA
5 Department of Pharmaceutical Science Research, School of Pharmacy, Marshall University, Huntington WV, USA

Article Metrics

CrossRef Citations:
Total Statistics:

Full-Text HTML Views: 1625
Abstract HTML Views: 616
PDF Downloads: 310
Total Views/Downloads: 2551
Unique Statistics:

Full-Text HTML Views: 839
Abstract HTML Views: 378
PDF Downloads: 212
Total Views/Downloads: 1429

Creative Commons License
© Fannin et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Center for Diagnostic Nanosystems, BBSC 241R, Department of Pharmaceutical Science Research, 1700 3rd Ave.Department of Biological Sciences, 1 John Marshall Drive, Marshall University, Huntington, WV 25755-1090; Fax: 304-692-3267; E-mail:
^ These authors equally contributed to this article.


Oxidative-nitrosative stress may play a role in age-associated cardiovascular disease as implied by recent studies.However, limited research has been conducted using aged female rodent models. In this study, we examined hearts obtained from 6-, 26-, and 30-month old female Fischer 344/Nnia x Brown Norway/BiNia (F344xBN) rats in order to examine how aging affects levels of cardiac oxidative-nitrosative stress and apoptosis. Oxidative (superoxide anion and 4-HNE) and nitrosative (protein nitrosylation) stress markers were increased 180 ± 17 %, 110 ± 3 %, and 14 ± 2 %, respectively in 30-month hearts compared to the hearts of 6-month female rats. Coincident with these changes in oxidative-nitrosative stress, aging was also found to be associated with increases in the number of Tdt-mediated dUTP nick labeling (TUNEL)-positive cardiomyocytes, alterations in the Bax/Bcl-2 ratio, and elevated cleavage of caspase-3. Regression analysis demonstrates significant correlation in the age-associated changes markers of oxidative–nitrosative stress with changes in apoptotic signaling. The findings from this descriptive study imply that age-associated increases in mitochondrial-mediated apoptosis may be associated with the increase in oxidative-nitrosative stress in the aging F344xBN female heart.

Keywords: : Heart, Aging, Female, ROS..