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Chronic acetaminophen attenuates age-associated increases in cardiac ROS and apoptosis in the Fischer Brown Norway rat

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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-3β. 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.

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Acknowledgments

Funding for this work was provided in part from a grant to ERB from Mc Neil Pharmaceuticals.

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Authors and Affiliations

  1. Department of Pharmacology, Physiology and Toxicology, Marshall University, Huntington, WV, USA

    Sunil K. Kakarla, Jacqueline C. Fannin, Anjaiah Katta, Siva K. Nalabotu & Eric R. Blough

  2. Laboratory of Molecular Physiology, Department of Biological Sciences, Robert C. Byrd Biotechnology Science Center, Marshall University, 1700 3rd Ave, Suite 311, Room 241N, Huntington, 25755-1090, WV, USA

    Saba Keshavarzian, Satyanarayana Paturi, Miaozong Wu, Kevin M. Rice & Eric R. Blough

  3. Department of Pathology, Marshall University, Huntington, WV, USA

    Ernest M. Walker Jr.

  4. Department of Exercise Physiology, Marshall University, Huntington, WV, USA

    Eric R. Blough

  5. Charleston Area Medical Center, Charleston, WV, USA

    Kamran Manzoor

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  1. Sunil K. Kakarla
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  2. Jacqueline C. Fannin
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  3. Saba Keshavarzian
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Correspondence to Eric R. Blough.

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Kakarla, S.K., Fannin, J.C., Keshavarzian, S. et al. Chronic acetaminophen attenuates age-associated increases in cardiac ROS and apoptosis in the Fischer Brown Norway rat. Basic Res Cardiol 105, 535–544 (2010). https://doi.org/10.1007/s00395-010-0094-3

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  • DOI: https://doi.org/10.1007/s00395-010-0094-3

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