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

Porto, Hellen Karine Paes; Grando, Marcella Daruge; Ramalho, Leandra Náira Zambelli; Valadares, Marize Campos; Bendhack, Lusiane Maria; Batista, Aline Carvalho; Rocha, Matheus Lavorenti

doi:10.1007/s00204-019-02463-0

Cited by 16 publications

(19 citation statements)

References 44 publications

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“…It has been shown that rats are more resistant to acetaminophen damage than mice [53]. Despite this observation, the presence of oxidative stress in the APAP-induced toxicity model in rats has broadly been demonstrated [54–56], regardless of the severity of the injury between species. Therefore, this experimental model in rats is still valid to test the antioxidant properties of CeO 2 NPs treatment on liver regeneration after drug-induced injury.…”

Section: Discussionmentioning

confidence: 99%

Cerium oxide nanoparticles improve liver regeneration after acetaminophen-induced liver injury and partial hepatectomy in rats

et al. 2019

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Background and aimsCerium oxide nanoparticles are effective scavengers of reactive oxygen species and have been proposed as a treatment for oxidative stress-related diseases. Consequently, we aimed to investigate the effect of these nanoparticles on hepatic regeneration after liver injury by partial hepatectomy and acetaminophen overdose.MethodsAll the in vitro experiments were performed in HepG2 cells. For the acetaminophen and partial hepatectomy experimental models, male Wistar rats were divided into three groups: (1) nanoparticles group, which received 0.1 mg/kg cerium nanoparticles i.v. twice a week for 2 weeks before 1 g/kg acetaminophen treatment, (2) N-acetyl-cysteine group, which received 300 mg/kg of N-acetyl-cysteine i.p. 1 h after APAP treatment and (3) partial hepatectomy group, which received the same nanoparticles treatment before partial hepatectomy. Each group was matched with vehicle-controlled rats.ResultsIn the partial hepatectomy model, rats treated with cerium oxide nanoparticles showed a significant increase in liver regeneration, compared with control rats. In the acetaminophen experimental model, nanoparticles and N-acetyl-cysteine treatments decreased early liver damage in hepatic tissue. However, only the effect of cerium oxide nanoparticles was associated with a significant increment in hepatocellular proliferation. This treatment also reduced stress markers and increased cell cycle progression in hepatocytes and the activation of the transcription factor NF-κB in vitro and in vivo.ConclusionsOur results demonstrate that the nanomaterial cerium oxide, besides their known antioxidant capacities, can enhance hepatocellular proliferation in experimental models of liver regeneration and drug-induced hepatotoxicity.

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Section: Discussionmentioning

confidence: 99%

Cerium oxide nanoparticles improve liver regeneration after acetaminophen-induced liver injury and partial hepatectomy in rats

et al. 2019

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“…31 In our findings, 2 weeks of PAR exposure impairs endothelium-dependent and endothelium-independent vasorelaxation, as previously shown by our group. 15 These results cannot be attributed to inhibition of the COX enzymes by PAR, since COX inhibition does not prejudice vascular relaxation mediated by endothelium. 32,33 To the contrary, COX inhibition seems to improve the vascular relaxation induced by endothelial NO.…”

Section: Discussionmentioning

confidence: 97%

“…Treatment with antioxidant compounds (including tiron and vitamin C) has proved effective in re-establishing blood vessel dilatation in environments of high oxidative stress. 15,42 Vascular GSH levels were determined to ascertain whether there were differences in its depletion in the trained or sedentary rats after PAR exposure. Some studies have shown an increase in lipid peroxidation and a decrease in GSH in the blood and target organs like the kidney and liver of PAR-treated rats.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, the cardiovascular system is quite sensitive to increases in oxidative stress, leading to impairment in vascular relaxation, cardiovascular remodelling and atherosclerosis 13,14 . Lately, we have reported that chronic exposure to PAR leads to toxic effects in the cardiovascular system and impaired vasodilation in rats exposed to PAR 15 …”

Section: Introductionmentioning

confidence: 99%

“…13,14 Lately, we have reported that chronic exposure to PAR leads to toxic effects in the cardiovascular system and impaired vasodilation in rats exposed to PAR. 15 Exercise training can improve cardiovascular performance, leading to increased cardiac pumping efficacy and vascular relaxation. 16,17 Studies have shown that in situations of increased oxidative stress, such as hypertension or diabetes, exercise training reduces the damage caused by oxidative stress in the cardiovascular system.…”

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Paracetamol‐induced metabolic and cardiovascular changes are prevented by exercise training

Ayres

Porto

Andrade

et al. 2020

Basic Clin Pharma Tox

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Paracetamol (PAR), also named acetaminophen, has been the most frequently consumed non-prescription drug in the world for several decades. It is the first line of non-steroidal anti-inflammatory drugs (NSAID) used for a large variety of clinical management of pain and fever, from the simple cold and migraines to osteoarthrosis and cancer. Given the easy accessibility and low price, approximately 10%-15% of patients overdose and need to be hospitalized for PAR intoxication, affecting 30 000 patients annually in the USA alone. 1 Hepatotoxicity and renal damage are the most important toxic effects reported from high-dose PAR. 2 However, in the last years, a number of studies have gradually revealed the side effects of this drug on many systems, namely the cardiovascular and respiratory systems. 3-5 Chan et al 6 demonstrated increased risk of vascular disorders like stroke and myocardial infarction after PAR use. This phenomenon has also been

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Emodin Attenuates Acetaminophen-Induced Hepatotoxicity via the cGAS-STING Pathway

et al. 2021

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

Cited by 16 publications

References 44 publications

Cerium oxide nanoparticles improve liver regeneration after acetaminophen-induced liver injury and partial hepatectomy in rats

Cerium oxide nanoparticles improve liver regeneration after acetaminophen-induced liver injury and partial hepatectomy in rats

Paracetamol‐induced metabolic and cardiovascular changes are prevented by exercise training

Emodin Attenuates Acetaminophen-Induced Hepatotoxicity via the cGAS-STING Pathway

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