Archives of Toxicology

, Volume 93, Issue 7, pp 1955–1964 | Cite as

Exposure to acetaminophen impairs vasodilation, increases oxidative stress and changes arterial morphology of rats

  • Hellen Karine Paes Porto
  • Marcella Daruge Grando
  • Leandra Naira Zambelli Ramalho
  • Marize Campos Valadares
  • Lusiane Maria Bendhack
  • Aline Carvalho Batista
  • Matheus Lavorenti RochaEmail author
Organ Toxicity and Mechanisms


Acetaminophen (APAP) is one of the most widely consumed drugs in the world. Studies have shown renal and hepatic damage as the direct result of high oxidative stress induced by APAP. Since the cardiovascular system is sensitive to oxidative stress and literature describes increased cardiovascular dysfunction in APAP consumers, this work aimed to evaluate harmful effects of APAP on the vascular system. Rats were exposed to APAP (400 mg/kg/day in drinking water) for 14 days. Plasma and aortas were collected and stored in − 80 °C and a selection of arteries was prepared for isometric tension recordings, morphological, immunohistochemical and protein expression analysis. The APAP-treated group presented increased transaminases (ALT/AST) and malondialdehyde levels in the plasma compared to controls. Lipid peroxidation, glutathione reductase and superoxide dismutase levels were increased in the plasma and arteries of the APAP group. Nevertheless, glutathione level was reduced as compared to control group. The vasodilation response to acetylcholine and sodium nitroprusside (0.1 nM to 10 µM) was also impaired after APAP treatment; however, the vascular relaxation was restored after treatment with vitamin C (100 µM). Arteries from the APAP group presented reduced wall thickness, collagen deposition, elastic fibers and increased immunoreactivity to nitrotyrosine. eNOS and sGC protein expression remained unchanged and were at similar levels as controls. These findings showed higher oxidative stress and impaired vasodilation in rats exposed to APAP. Furthermore, arteries presented reduced cell layers, collagen, elastin deposition and significantly increased immunoreactivity to nitrotyrosine after APAP treatment.


Acetaminophen Oxidative stress Artery Vascular relaxation 



Aline C. Batista, Lusiane M. Bendhack, Marize C. Valadares, Matheus L. Rocha are researchers fellow of Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brazil).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest, financial or otherwise.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted (protocol number 083/16).


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Hellen Karine Paes Porto
    • 1
  • Marcella Daruge Grando
    • 2
  • Leandra Naira Zambelli Ramalho
    • 3
  • Marize Campos Valadares
    • 1
  • Lusiane Maria Bendhack
    • 2
  • Aline Carvalho Batista
    • 4
  • Matheus Lavorenti Rocha
    • 1
    Email author
  1. 1.Laboratory of Pharmacology, Faculty of PharmacyFederal University of GoiasGoiâniaBrazil
  2. 2.Department of Physics and Chemistry, Faculty of Pharmaceutical SciencesFCFRP/USPRibeirão PretoBrazil
  3. 3.Department of Pathology and Legal Medicine, Medical SchoolFMRP/USPRibeirão PretoBrazil
  4. 4.Laboratory of Pathology, Faculty of DentistryFederal University of GoiasGoiâniaBrazil

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