Exposure to acetaminophen impairs vasodilation, increases oxidative stress and changes arterial morphology of rats
- 247 Downloads
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.
KeywordsAcetaminophen 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.
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).
- Rubbo H, Radi R, Trujillo M et al (1994) Nitric oxide regulation of superoxide and peroxynitrite-dependent lipid-peroxidation. Formation of novel nitrogen-containing oxidized lipid derivatives. J Biol Chem 269:26066–26075Google Scholar
- Verma S, Raj SR, Shewchuk L, Mather KJ, Anderson TJ (2001) Cyclooxygenase-2 blockade does not impair endothelial vasodilator function in healthy volunteers: randomized evaluation of rofecoxib versus naproxen on endothelium-dependent vasodilatation. Circulation 104(24):2879–2882CrossRefPubMedGoogle Scholar