MicroRNA from a 12-h versus 20-h acetylcysteine infusion for paracetamol overdose

Wong, Anselm; Nejad, Charlotte; Gantier, Michael P.; Choy, Kay Weng; Doery, James C.G.; Graudins, Andis

doi:10.1177/0960327119833740

Cited by 6 publications

(7 citation statements)

References 17 publications

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“…Others, like Wong et al [ 90 , 91 ], went further to assess the impact of dosing differently with NAC on paracetamol overdose. Here, they showed that in subjects receiving 12 h NAC regimen (200 mg/kg over 4 h, 50 mg/kg over 8 h) had similar circulating metabolite concentrations compared to a 20 h regimen in selected subjects with a low risk of hepatotoxicity.…”

Section: Protective Effects Of N-acetyl Cysteine Against Drug-induced Liver Injurymentioning

confidence: 99%

“…Here, they showed that in subjects receiving 12 h NAC regimen (200 mg/kg over 4 h, 50 mg/kg over 8 h) had similar circulating metabolite concentrations compared to a 20 h regimen in selected subjects with a low risk of hepatotoxicity. Also, there was no observed liver injury or any effect on levels of ALT or miR-122 expression [ 90 , 91 ]. Besides assessing the impact of different doses, others reported on how NAC affects paracetamol when used in combination with other therapies.…”

Section: Protective Effects Of N-acetyl Cysteine Against Drug-induced Liver Injurymentioning

confidence: 99%

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Drug‐Induced Liver Injury: Clinical Evidence of N‐Acetyl Cysteine Protective Effects

Ntamo

Ziqubu

Chellan

et al. 2021

Oxidative Medicine and Cellular Longevity

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Oxidative stress is a key pathological feature implicated in both acute and chronic liver diseases, including drug-induced liver injury (DILI). The latter describes hepatic injury arising as a direct toxic effect of administered drugs or their metabolites. Although still underreported, DILI remains a significant cause of liver failure, especially in developed nations. Currently, it is understood that mitochondrial-generated oxidative stress and abnormalities in phase I/II metabolism, leading to glutathione (GSH) suppression, drive the onset of DILI. N-Acetyl cysteine (NAC) has attracted a lot of interest as a therapeutic agent against DILI because of its strong antioxidant properties, especially in relation to enhancing endogenous GSH content to counteract oxidative stress. Thus, in addition to updating information on the pathophysiological mechanisms implicated in oxidative-induced hepatic injury, the current review critically discusses clinical evidence on the protective effects of NAC against DILI, including the reduction of patient mortality. Besides injury caused by paracetamol, NAC can also improve liver function in relation to other forms of liver injury such as those induced by excessive alcohol intake. The implicated therapeutic mechanisms of NAC extend from enhancing hepatic GSH levels to reducing biomarkers of paracetamol toxicity such as keratin-18 and circulating caspase-cleaved cytokeratin-18. However, there is still lack of evidence confirming the benefits of using NAC in combination with other therapies in patients with DILI.

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Section: Protective Effects Of N-acetyl Cysteine Against Drug-induced Liver Injurymentioning

confidence: 99%

Section: Protective Effects Of N-acetyl Cysteine Against Drug-induced Liver Injurymentioning

confidence: 99%

Drug‐Induced Liver Injury: Clinical Evidence of N‐Acetyl Cysteine Protective Effects

Ntamo

Ziqubu

Chellan

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…It is worth noting that the doses chosen for NAC and SIL, that is, 200 mg/kg, were due to two factors, one being a dose with a known hepatoprotective effect in others one-hit models of liver injury for both compounds [15][16][17][18][19][20] and because it is a dose that can be transferred to the clinic, given that the equivalent dose extrapolated allometrically would be 49 mg/kg for humans.…”

Section: Discussionmentioning

confidence: 99%

“…The dose of SIL and NAC chosen was based in the dose with a known hepatoprotective effect in others one-hit models of liver injury for both compounds. [15][16][17][18][19][20] The weight of each animal was assessed during this time. Animals that had been administered xylazine (10 mg/kg) and ketamine (50 mg/kg) for anesthesia were punctured in the heart to collect blood.…”

Section: Lps and Ethanol Induce Liver Damagementioning

confidence: 99%

Are silymarin and N‐acetylcysteine able to prevent liver damage mediated by multiple factors? Findings against ethanol plus LPS‐induced liver injury in mice

dos Santos,

França,

Venzon

et al. 2023

J Biochem & Molecular Tox

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This study investigated the effect of N‐acetylcysteine (NAC) and silymarin (SIL) in the liver of mice exposed to ethanol and lipopolysaccharides (LPS). Mice were divided into four groups (n = 6): naive, vehicle, NAC (200 mg/kg), and SIL (200 mg/kg). Treatments were given orally (po) once daily for 10 days. Liver injury was induced by administration of ethanol (30%, po) for 10 days, once daily, followed by a single administration of LPS (2 mg/kg, ip) 24 h before euthanasia. After the treatment period, animals were euthanized, and liver and blood samples were collected. NAC, but not SIL, prevented the increase in oxalacetic glutamic transaminase (OGT) and pyruvic glutamic transaminase (PGT) serum levels. NAC and SIL did not restore levels of reduced glutathione or hepatic malonaldehyde. The treatments with NAC or SIL showed no difference in the activity of glutathione S‐transferase, superoxide dismutase, and catalase compared to vehicle group. Myeloperoxidase and N‐acetylglucosaminidase activities are increased, as well as the IL‐6 and IL‐10 levels in the liver. The treatment with NAC, but not SIL, reduced the N‐acetylglucosamines activity and the IL‐6 and IL‐10 amount in the liver. Histological findings revealed microsteatosis in the vehicle group, which was not prevented by SIL but was partially reduced in animals receiving NAC. Unlike other liver injury models, NAC (200 mg/kg) or SIL (200 mg/kg) did not positively affect antioxidant patterns in liver tissue of animals exposed to ethanol plus LPS, but NAC treatment displays anti‐inflammatory properties in this model.

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“…Significant changes in circulating miRNA profiles of various biologic matrices (e.g., blood, urine) have been demonstrated in mouse and rat models of acetaminophen toxicity [10][11][12]. In humans, key miRNAs have been notably upregulated in urine [13], hepatocytes [14,15], and blood [15][16][17][18][19][20]. Human studies have largely focused on liver-associated miRNAs, specifically miR-122, which has repeatedly been found to be elevated in acetaminophen hepatotoxicity [21,22].…”

Section: Introductionmentioning

confidence: 99%

Circulating microRNA Profiles in Acetaminophen Toxicity

et al. 2019

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Introduction Acetaminophen toxicity has been associated with elevation of microRNAs. The present study was to evaluate overall microRNA profiles and previously identified microRNAs to differentiate acetaminophen (APAP) toxicity from other causes of transaminase elevation. Methods This was an observational study of adults with presumed acetaminophen toxicity at presentation. Serum samples were collected every 12 hours during hospitalization. Total miRNAs were extracted from plasma and levels of 327 microRNAs were quantified using real-time polymerase chain reaction. A standard measure of miRNA expression (delta-delta cycle threshold) was calculated for each microRNAs. A two-level cluster analysis was performed using a random k-means algorithm. Demographic and clinical characteristics of each cluster were compared using ANOVA, Wilcoxon rank sum, Kruskal-Wallis, and chi-square tests. Performance of specific miRNAs of interest was also evaluated. Results Twenty-seven subjects were enrolled (21 with a final diagnosis of acetaminophen toxicity), and a total of 61 samples were analyzed. Five clusters were identified, two of which demonstrated clear clinical patterns and included specific elevated miRNAs previously reported to be elevated in APAP toxicity patients. Features associated with clusters 1 and 5 included confirmed acetaminophen toxicity, high peak alanine aminotransferase, and late presentation. Clusters 2-4 contained lower peak microRNAs, lower peak alanine aminotransferase, and heterogeneous clinical characteristics. Conclusions Severe cases of acetaminophen toxicity showed two distinct patterns of microRNA elevation which were similar to previous work, while less severe cases were difficult to distinguish from non-acetaminophen-associated cases. Further work is needed to incorporate microRNA profiles into the diagnostic algorithm of acetaminophen toxicity.

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MicroRNA from a 12-h versus 20-h acetylcysteine infusion for paracetamol overdose

Cited by 6 publications

References 17 publications

Drug‐Induced Liver Injury: Clinical Evidence of N‐Acetyl Cysteine Protective Effects

Drug‐Induced Liver Injury: Clinical Evidence of N‐Acetyl Cysteine Protective Effects

Are silymarin and N‐acetylcysteine able to prevent liver damage mediated by multiple factors? Findings against ethanol plus LPS‐induced liver injury in mice

Circulating microRNA Profiles in Acetaminophen Toxicity

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