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

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Abstract

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.

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Acknowledgements

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).

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Authors and Affiliations

  1. Laboratory of Pharmacology, Faculty of Pharmacy, Federal University of Goias, Av. Universitária com 1a Avenida s/n, Setor Universitário, Goiânia, GO, CEP 74605-220, Brazil

    Hellen Karine Paes Porto, Marize Campos Valadares & Matheus Lavorenti Rocha

  2. Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences, FCFRP/USP, Ribeirão Preto, SP, Brazil

    Marcella Daruge Grando & Lusiane Maria Bendhack

  3. Department of Pathology and Legal Medicine, Medical School, FMRP/USP, Ribeirão Preto, SP, Brazil

    Leandra Naira Zambelli Ramalho

  4. Laboratory of Pathology, Faculty of Dentistry, Federal University of Goias, Goiânia, Brazil

    Aline Carvalho Batista

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  1. Hellen Karine Paes Porto
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Porto, H.K.P., Grando, M.D., Ramalho, L.N.Z. et al. Exposure to acetaminophen impairs vasodilation, increases oxidative stress and changes arterial morphology of rats. Arch Toxicol 93, 1955–1964 (2019). https://doi.org/10.1007/s00204-019-02463-0

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