A Review of Bioinformatics Tools to Understand Acetaminophen-Alcohol Interaction

Hedgpeth, Bryan M.; Missall, Roy; Bambaci, Anna; Smolen, Matthew; Yavuz, Sevgi; Cottrell, Jessica; Chu, Tin-Chun; Chang, Sulie L.

doi:10.3390/medicines6030079

Cited by 5 publications

(3 citation statements)

References 30 publications

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“…NAPQI is a reactive metabolite formed by the action of cytochrome P450 on paracetamol (acetaminophen). Glutathione conjugates to NAPQI and the resulting product is excreted [ 24 ]. Many enzymes use GSH as a cofactor or substrate.…”

Section: The Protective Actions Of Gshmentioning

confidence: 99%

The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19

2020

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The novel COVID-19 pandemic is affecting the world’s population differently: mostly in the presence of conditions such as aging, diabetes and hypertension the virus triggers a lethal cytokine storm and patients die from acute respiratory distress syndrome, whereas in many cases the disease has a mild or even asymptomatic progression. A common denominator in all conditions associated with COVID-19 appears to be the impaired redox homeostasis responsible for reactive oxygen species (ROS) accumulation; therefore, levels of glutathione (GSH), the key anti-oxidant guardian in all tissues, could be critical in extinguishing the exacerbated inflammation that triggers organ failure in COVID-19. The present review provides a biochemical investigation of the mechanisms leading to deadly inflammation in severe COVID-19, counterbalanced by GSH. The pathways competing for GSH are described to illustrate the events concurring to cause a depletion of endogenous GSH stocks. Drawing on evidence from literature that demonstrates the reduced levels of GSH in the main conditions clinically associated with severe disease, we highlight the relevance of restoring GSH levels in the attempt to protect the most vulnerable subjects from severe symptoms of COVID-19. Finally, we discuss the current data about the feasibility of increasing GSH levels, which could be used to prevent and subdue the disease.

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Section: The Protective Actions Of Gshmentioning

confidence: 99%

The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19

2020

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“…Cellular CYP2E1 is known to mediate prolonged alcohol and APAP induced toxicity in hepatic and extra-hepatic cells. Chronic ethanol intake may enhance APAP toxicity by producing a persistent up-regulation of CYP2E1, as well as depleting GSH stores [13,14]. In the current study, APAP and ROX were administrated to rats, with the dose calculated to be standard through conversion of human body surface area to rat body surface area.…”

Section: Discussionmentioning

confidence: 99%

Drug-drug interaction of acetaminophen and roxithromycin with the cocktail of cytochrome P450 and hepatotoxicity in rats

2020

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Acetaminophen (APAP) and roxithromycin (ROX) are often used in combination in clinical practice. To evaluate their drug-drug interactions (DDIs) and the hepatotoxicity of co-administration, rats were randomly separated into four groups: Control, APAP (50 mg/kg), ROX (5.5 mg/kg) and APAP-ROX (50 mg/kg and 5.5 mg/kg, respectively). The pharmacokinetic parameters between APAP and ROX were assayed by HPLC, and a cocktail method was used to evaluate the activities of cytochrome (CYP) 450. The liver microsome CYP2E1 protein was detected using Western blot. The levels of plasma parameters, mRNA levels of inflammatory factors (TNF-α, INF-γ, VCAM-1, CXCL-1 and STAT-3) and antioxidant factors (Nrf-2, GSTA, GCLC-1, HO-1 and NQO1) were determined using real-time PCR, along with the observation on histopathological changes in the liver tissue. APAP and ROX co-treatment significantly increased CYP2E1 activity, decreased CYP2D6 activity and prolonged APAP and ROX clearance. Co-treatment increased mRNA expressions of TNF-α, NQO1 and MDA while decreasing GPX and SOD levels. Histopathological evidence showed the changes of liver tissues in terms of structure, size and tight arrangement. This study confirmed that a combination of APAP and ROX inhibited APAP metabolism and that the peak concentration of ROX was delayed. The resulting high level of CYP2E1 may induce oxidative stress and cause liver damage.

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“…The conjugation process is represented by N-Acetyl-P-Benzoquinone Imine (NAPQI) metabolism as a reactive metabolite produced by cytochrome P450 action on paracetamol (acetaminophen). After combining glutathione with NAPQI, the resulting product is excreted [174].…”

Section: Glutathionementioning

confidence: 99%

A Promising Approach to Improving COVID-19 Symptoms: Using Antioxidant Supplements

Shahbaz

Naderi

Hedayati

et al. 2021

The Journal of Qazvin University of Medical Sciences

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Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) that causes COVID-19 could progress to acute respiratory distress syndrome (ARDS). The immune cells' migration in response to virus lead to cell death by releasing oxidizing free radicals. These oxidizing free radicals mediate NF-κB activation and induce transcription of cytokine-producing genes that eventually a cytokine storm ensues, leading to septic shock. The over-expression of oxidative stress and enhancing ROS and RNS production activates transcription factors like NF-κB, so repeating this cycle intensifies the host inflammatory responses. In this way, antioxidants as compounds that inhibit oxidation by terminating chain reactions are suggested for alleviating the COVID-19 demonstration. In the present review study, the pathogenesis of the virus, the virus immunopathology, the balance between immune responses and oxidative stress are discussed. Also in this review, due to the importance of oxidative stress in the pathogenesis of the disease, some of the most important antioxidant agents whose therapeutic effects have been shown in improving many viral infections, ARDS, and acute lung injury, are recommended to improve the patient’s condition infected with SARS-CoV-2. Besides, the last COVID-19 clinical studies in this field are summarized in this review article. These studies described that melatonin through promoting sleep quality by decreasing vascular permeability, reducing anxiety, and regulating blood pressure; and vitamin C through decreasing the mortality rates and the requirement for mechanical ventilation; and Glutathione through decreasing respiratory distress in the pneumonia of COVID-19 patients; and higher selenium levels could improve the COVID-19 patients' clinical outcomes

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A Review of Bioinformatics Tools to Understand Acetaminophen-Alcohol Interaction

Cited by 5 publications

References 30 publications

The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19

The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19

Drug-drug interaction of acetaminophen and roxithromycin with the cocktail of cytochrome P450 and hepatotoxicity in rats

A Promising Approach to Improving COVID-19 Symptoms: Using Antioxidant Supplements

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