Acetaminophen Overdose Research Articles

Implementation of a pharmacist toxicology service on treatment of paracetamol (acetaminophen) overdose

Introduction Paracetamol is a leading cause of fatality following a toxic ingestion. Individualized treatment is imperative in improving outcomes. Acetylcysteine is the standard of care for paracetamol overdose. Laboratory values and other clinical criteria can be used to guide treatment duration. Our hospital’s protocol allows paracetamol overdose to be managed by the emergency department pharmacists. The purpose of this study was to evaluate the effect of a pharmacist toxicology service on the management of paracetamol overdose. Methods This was a single center, retrospective, cohort evaluation. All patients receiving acetylcysteine were divided into pre- and post-implementation groups with data obtained from August 1, 2013 to January 14, 2018 and January 15, 2018 to September 30, 2021, respectively. The primary outcome was the frequency of individualized acetylcysteine therapy. Results A total of 238 patients were screened for inclusion in the study with 120 patients included in the final analysis. There were 60 patients included in each cohort. The frequency of individualized acetylcysteine therapy was significantly higher in the post-implementation group versus the pre-implementation group (85% vs. 60% [95% CI 9.1–39.4; P = 0.002]). Conclusions The implementation of a pharmacist toxicology service correlated with increased poison center consultation as well as increased frequency of individualized acetylcysteine therapy and decreased number of missed acetylcysteine doses.

Construction of functionalized carbon nanotube@metal oxide nanocomposite for high-performance electrochemical measurement of antipyretic drug in water samples.

Acetaminophen (AP) acts as supportive clinical therapy for fever and dysmenorrhea. An overdose of AP may result in severe adverse diseases, such as liver dysfunction. In addition, AP is a key-listed environmental pollutant, which is difficult to degrade in the environment and has serious effects on living bodies. Therefore, the simple and quantitative determination of AP is highly relevant today. In this work, tin dioxide (SnO2) nanoparticles with functionalized multi-walled carbon nanotube (f-MWCNT) as a hybrid composite were prepared by hydrothermal-assisted synthesis. The composite material was characterized by various spectral, morphological, and electrochemical tests. Electrochemical investigations were conducted using a SnO2@f-MWCNT-reinforced electrode for the detection of AP. The composite electrode exhibited better functional properties, which facilitated electron transfer and enhanced electrical conductivity. The calculated low detection limit (LOD) of 0.36 nM is with a wide linear range of concentration from 0.001 to 673 µM. Additionally, the SnO2@f-MWCNT-modified electrode exhibited good anti-interference capability, repeatability, reproducibility, storage, and operational stability. The developed SnO2@f-MWCNT-modified electrode was applied to practical analysis in diverse water matrices (river, drinking, and pond) with acceptable recovery percentages. A synthesized nanoscale metal oxide electrocatalyst is of great interest and an active research area that serves as a foundation for the development of new, cost-effective electrochemical antibiotic drug sensors.

Prevalence and factors associated with non-suicidal self-Injury and suicidality in children and adolescent attending Emergency department in Oman

IntroductionNon-suicidal self-Injury (NSSI) and suicidality are common reasons for emergency presentations in child and adolescent psychiatry (1). NSSI is defined as intentional destruction of one’s body tissue without suicidal intent and has a prevalence rate in adolescents of approximately 30–40% in clinical samples (2). Suicide prevalence is around 24–33% (3).There are many factors leading to suicidal or self-harming behavior. A prior history of self-injurious behavior is one of the strongest predictors of future suicidal behavior, both cross-sectionally and longitudinally (6) . Additionally, longitudinal studies have found that a previous suicide attempt increases the risk of a future suicide attempt threefold.Suicide and NSSI have a significant impact on families and communities. Hence, considerable required clinical attention is warranted to develop preventive strategies.ObjectivesThe aim of this study is to investigate the prevalence of non-suicidal self-Injury (NSSI) and suicidality among children and adolescents presenting in emergency department of the tertiary psychiatric services and to study their demographic and clinical characteristics.MethodsThis is a retrospective cross-sectional analytical study included all children and adolescent patients attended the emergency department at Sultan Qaboos University Hospital between June 2021 to March 2016. The data was collected using the hospital´s electronic database to retrieve the medical records of children and adolescents who visited the emergency department. Patients who were 18 years of the age or younger were included in the study. The included patients must had been evaluated by psychiatrist during their presentations in the emergency department.ResultsDuring the 63 months of observation, 114 patients attended the emergency department and required psychiatric evaluation, 44.7%(n=51) of patients presented with NSSI and/or SA. The mean age was 15.7. 80.4%(n=41) were females while 19.6%(n=10) were males. 37.3% had a primary diagnosis of major depressive disorder (MDD) and 21.5% had comorbid medical illness. 44% of suicidal attempts were with drug overdose, mostly paracetamol overdose, while the most used method for NSSI was cutting the body with a razor, 57%.19 patients had a primary diagnosis of major depressive disorder, 17 patients had no clear diagnosis at presentation.22% of the patients had other medical comorbidities, 5 patients with epilepsy. 51% of the patients had positive family history of mental illness.ConclusionsConsidering that NSSI and suicidality were found to be the main reasons for presenting to a child and adolescent emergency psychiatric service, it seems crucial for physicians at PEDs to provide proper crisis intervention and referral to mental health services when appropriate. Early identification of risk factors is highly recommended.Disclosure of InterestNone Declared

Caesalpinia bonducella Counteracts Paracetamol-Instigated Hepatic Toxicity via Modulating TNF-α and IL-6/10 Expression and Bcl-2 and Caspase-8/3 Signalling.

Paracetamol is the most predominantly used antipyretic and analgesic drug. As paracetamol is metabolised mostly in the liver, both deliberate and unintentional overdoses of paracetamol are reported to provoke severe hepatotoxicity, including liver failure.Caesalpinia bonducellaseed is well known for its medicinal and therapeutic properties. However, there is no report on its potential protective effects against paracetamol-instigated hepatotoxicity. Therefore, we studied the protective effects of aqueous seed extract ofCaesalpinia bonducella(ASECB) on paracetamol-instigated hepatotoxicity in rats. Thirty female albino rats were divided into five groups: control, paracetamol-intoxicated, ASECB + paracetamol, silymarin + paracetamol, and ASECB alone. The rats were assessed for liver enzyme markers (alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase), antioxidant activity (superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase), lipid peroxidation (malondialdehyde), histopathological, cytokine levels (pro-inflammatory cytokines TNF-α and IL-6, and anti-inflammatory cytokine IL-10), and protein expression (pro-apoptotic markers caspase 3 and caspase 8 and anti-apoptotic marker Bcl-2) after the 8-day study period. Repercussions of paracetamol intoxication induced upregulation of liver enzyme markers, antioxidant depletion, malondialdehyde production, decreased expression of Bcl-2 and IL-10, and overexpression of apoptotic and pro-inflammatory mediators, which were attenuated by pre-treatment with ASECB. ASECB markedly mitigated paracetamol-instigated liver injury by suppressing caspase-8/3 signalling and inflammatory infiltration in liver tissue by significantly reducing TNF-α and IL-6. In conclusion, ASECB pre-treatment exerts potent liver protection against paracetamol-instigated hepatotoxicity evidenced by mitigation of oxidative stress, lipid peroxidation, inflammation, and apoptosis.

Concerns about intentional paracetamol poisoning, maximum pack sizes to be reduced in Australia

Concerns about intentional paracetamol poisoning, maximum pack sizes to be reduced in Australia

The hepatoprotective candidates by synergistic formula of marine and terrestrial against Acetaminophen toxicity using in-vitro, in-vivo, and in silico screening approach

BackgroundOne of the most regularly used hepatotoxic medicines is paracetamol (acetaminophen, N-acetyl-p-aminophenol; APAP). It causes liver failure in overdoses but is safe at therapeutic dosages. Combination therapy combining many natural compounds with a synergistic impact as hepatoprotective agents has become an essential therapeutic method against various disorders. ObjectiveDue to the lack of literature on paracetamol's effects on hematological and hepatic status parameters in male albino mice, the main goal of this study was to compare the hepatoprotective activities of a mixture of three marine-derived polyphenolics and polysaccharides (Sargassum vulgare Bacillus oceanisediminis, and alginic acids) to Chrysanthemum extract and the mixture of them. MethodsSargassumvulgare, Bacillus Oceanisediminis, and alginate, as well as Chrysanthemum ethanol extracts, were tested for APAP-induced liver damage. Group 1 received saline solution subcutaneously, while Group 2 received 500 mg/kg body weight/day APAP intraperitoneal. Group 3 got 200 mg/day algal extract i.p. As in group 3, group 4 got an i.p. dose of 200 mg of algal extract before the APAP dose. This group was protected by Sargassum vulgare extract. Group 5: Received 200 mg/100 g/body of Bacillus oceanisediminis extracts i.p. for one week. Group 6: Received 200 mg/body of Bacillus oceanisediminis extract i.p. for one week before APAP treatment. Alginate (p200 mg/body weight/day) was given to Group 7. As in group 7, group 8 received 200 mg/body weight/day alginate extract i.p. before APAP. Group 9: Chrysanthemum extracts 200 mg/day for a week. Group 10: got an i.p. dose of Chrysanthemum extracts for one week before the APAP dose. Group 11: Four mixed extracts (Bacillus Oceanisediminis, Sargassum vulgare, Chrysanthemum, and alginate) were i.p200 mg/day for one week as a positive (+ve) control group. Group 12: Received i.p200 mg/kg combination extract for one week before APAP. ResultsDue to their synergistic antioxidant and anti-inflammatory actions, marine extracts and combinations of marine-derived extracts demonstrated a great effect against APAP toxicity, demonstrating hepatoprotective potential against APAP-induced liver damage. ConclusionThe synergy of the three marine-derived combinations may lead to novel liver toxicity prevention agents.

SNAPTIMED study: does the Scottish and Newcastle Antiemetic Protocol achieve timely intervention and management from the emergency department to discharge for paracetamol poisoning?

BackgroundThis study aimed to establish whether the modified 12-hour Scottish and Newcastle Antiemetic Protocol (SNAP) for paracetamol poisoning is associated with improvement in hospital length of stay (LoS), as well...

Sumc (Rhus coriaria L.) fruit ameliorates paracetamol-induced hepatotoxicity

Sumac [Rhus coriaria L. (Anacardiaceae)] is a widely used spice in the Middle East. In this study, the hepatoprotective effects of sumac fruit were evaluated using a rat model of paracetamol-induced liver injury. The experimental design relies on the pretreatment of rats with intraperitoneal sumac extract followed by a toxic dose of paracetamol. Tissue alterations, serum levels of oxidative stress markers, as well as gene expression of immunomarkers were evaluated. Rats pre-treated with sumac displayed attenuated signs of toxicity. Upon paracetamol intoxication, sumac-pretreated animals showed a minimal increase in liver enzyme levels. In parallel, serum albumin and total protein levels were close to normal. Moreover, pretreated sumac animals had preserved hepatocyte morphology, whereas unprotected animals had necrotic deformations. Importantly, these effects were dose-dependent and comparable to the silymarin-treated positive control group. In conclusion, sumac extract offers a potential hepatoprotective regimen against xenobiotic-induced hepatotoxicity and for oxidative stress management.

Assessment of Awareness about Paracetamol Toxicity and Paracetamol-Containing Drugs among the Public

Assessment of Awareness about Paracetamol Toxicity and Paracetamol-Containing Drugs among the Public

Role of NADPH Oxidase-Derived ROS-Mediated IL-6/STAT3 and MAPK/NF-κB Signaling Pathways in Protective Effect of Corilagin against Acetaminophen-Induced Liver Injury in Mice

Acetaminophen (APAP) overdose causes acute liver injury via oxidative stress, uncontrolled inflammatory response, and subsequent hepatocyte death. Nicotinamide adenine dinucleotide phosphate oxidase (NOX) is a potent source of cellular reactive oxygen species (ROS) and may contribute to oxidative stress in many inflammatory processes. Corilagin, a component of Phyllanthus urinaria, possesses antioxidant, anti-inflammatory, and hepatoprotective effects. We evaluated the mechanisms underlying the protective effect of corilagin against acetaminophen-induced liver injury. Mice were intraperitoneally administrated 300 mg/kg APAP or equal volume of saline (control), with or without various concentrations of corilagin (0, 1, 5, or 10 mg/kg) administered after 30 min. All animals were sacrificed 16 h after APAP administration, and serum and liver tissue assays including histology, immunohistochemistry, and Western blot assay were performed. Corilagin post-treatment significantly attenuated APAP-induced liver injury (p < 0.005), inflammatory cell infiltration, hepatic proinflammatory cytokine levels, and hepatic oxidative stress. Furthermore, corilagin attenuated the protein levels of NOX1, NOX2, signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) in APAP-induced liver injury. These results indicated that the antioxidant, anti-inflammatory, and protective effects of corilagin in APAP-induced liver injury might involve the regulation of interleukin (IL)-6/STAT3 and mitogen-activated protein kinase (MAPK)/NF-κB signaling pathways through NOX-derived ROS.

Piezo1 alleviates acetaminophen-induced acute liver injury by activating Nrf2 and reducing mitochondrial reactive oxygen species

Acetaminophen (APAP) overdose is the most common cause for acute liver failure (ALF) in the developed countries, with limited treatment options. Piezo1 is a mechanosensitive cation channel. We found that APAP caused upregulation of Piezo1 in both an APAP-induced acute liver injury (ALI) animal model and a mouse hepatocyte cell line AML12. Activation of Piezo1 by its activator Yoda1 reduced APAP-induced hepatotoxicity and ROS level. Mechanistically, activation of Piezo1 led to accumulation of the antioxidant regulator Nrf2 and upregulation of its target genes Nqo1 and Gsta1, while knockdown of Piezo1 downregulated this pathway. Finally, injection of Yoda1 decreased serum AST and ALT levels, reduced cell death and rescued liver injury in the APAP-induced ALI mouse model. Our findings suggested a previously undiscovered protective role of Piezo1 in APAP-induced ALI, which might shed light on a new therapeutic target for this disease.

A Massive Acetaminophen Overdose with Unusual Pharmacokinetics

A clinical case report demonstrates the importance of managing a massive overdose of immediate-release acetaminophen using the same approach reserved for an overdose involving an extended-release formulation because of altered pharmacokinetics. RésuméCet article présente un rapport de cas cliniques démontrant l’importance de traiter une surdose mas-sive d’acétaminophène à libération immédiate en utilisant la même approche que celle utilisée pour traiter une surdose mettant en cause une préparation à libération prolongée en raison de la modification de la pharmacocinétique.

Narirutin activates TFEB (transcription factor EB) to protect against Acetaminophen-induced liver injury by targeting PPP3/calcineurin

ABSTRACT Acetaminophen (APAP) overdose is the predominant cause of drug-induced liver injury worldwide. The macroautophagy/autophagy-lysosomal pathway (ALP) is involved in the APAP hepatotoxicity. TFEB (transcription factor EB) promotes the expression of genes related to autophagy and lysosomal biogenesis, thus, pharmacological activation of TFEB-mediated ALP may be an effective therapeutic approach for treating APAP-induced liver injury. We aimed to reveal the effects of narirutin (NR), the main bioactive constituents isolated from citrus peels, on APAP hepatotoxicity and to explore its underlying mechanism. Administration of NR enhanced activities of antioxidant enzymes, improved mitochondrial dysfunction and alleviated liver injury in APAP-treated mice, whereas NR did not affect APAP metabolism and MAPK/JNK activation. NR enhanced TFEB transcriptional activity and activated ALP in an MTOR complex 1 (MTORC1)-independent but PPP3/calcineurin-dependent manner. Moreover, knockout of Tfeb or knockdown of PPP3CB/CNA2 (protein phosphatase 3, catalytic subunit, beta isoform) in the liver abolished the beneficial effects of NR on APAP overdose. Mechanistically, NR bound to PPP3CB via PRO31, LYS61 and PRO347 residues and enhanced PPP3/calcineurin activity, thereby eliciting dephosphorylation of TFEB and promoting ALP, which alleviated APAP-induced oxidative stress and liver injury. Together, NR protects against APAP-induced liver injury by activating a PPP3/calcineurin-TFEB-ALP axis, indicating NR may be a potential agent for treating APAP overdose. Abbreviations: ALP: autophagy-lysosomal pathway; APAP: acetaminophen; APAP-AD: APAP-protein adducts; APAP-Cys: acetaminophen-cysteine adducts; CAT: catalase; CETSA: cellular thermal shift assay; CQ: chloroquine; CYP2E1: cytochrome P450, family 2, subfamily e, polypeptide 1; CYCS/Cyt c: cytochrome c, somatic; DARTS: drug affinity responsive target stability assay; ENGASE/NAG: endo-beta-N-acetylglucosaminidase; GOT1/AST: glutamic-oxaloacetic transaminase 1, soluble; GPT/ALT: glutamic pyruvic transaminase, soluble; GSH: glutathione; GPX/GSH-Px: glutathione peroxidase; KD: dissociation constant; Leu: leupeptin; MCOLN1: mucolipin 1; MTORC1: MTOR complex 1; NAC: N-acetylcysteine; NAPQI: N-acetyl-p-benzoquinoneimine; NFAT: nuclear factor of activated T cells; NR: narirutin; OA: okadaic acid; RRAG: Ras related GTP binding; ROS: reactive oxygen species; PPP3CB/CNA2: protein phosphatase 3, catalytic subunit, beta isoform; PPP3R1/CNB1: protein phosphatase 3, regulatory subunit B, alpha isoform (calcineurin B, type I); SOD: superoxide dismutase; SPR: surface plasmon resonance analysis; TFEB: transcription factor EB.

Active Pharmaceutical Ingredient and Impurity Profiling Paracetamol

The first paracetamol was created in 1877, or even 1852. In both the US and Europe, it is the most frequently prescribed drug for pain and fever. It is listed as one of the Essential Medicines by the World Health Organization. Tylenol and Panadol are just a couple of the brand names for the generic drug paracetamol, which is also sold under numerous names. It received more than 5 million prescriptions in 2020, ranking it as the 118th most popular drug in the country..Acetaminophen, usually referred to as paracetamol, is a drug used to treat fever and mild to moderate discomfort.Tylenol and Panadol are examples of popular brand names.The benefits of paracetamol use for fever are unclear because, at a typical dose, it only modestly lowers body temperature; in that regard, it is inferior than ibuprofen. Acute mild migraines may be helped by paracetamol, however recurring tension headaches may only be minimally relieved. Ibuprofen is superior to paracetamol in terms of effectiveness for post-surgical pain management. The medicine of choice for lowering fever is paracetamol. It’s unclear whether paracetamol has any advantages in musculoskeletal problems like osteoarthritis and backaches.When used to treat mild to moderate pain, paracetamol can help with headaches, muscle pains, minor arthritic pain, toothaches, and discomfort from the common cold, the flu, sprains, and dysmenorrhea. It is particularly advised for acute mild to moderate pain because there is little evidence to support its use in the treatment of chronic pain. At a dose of 4gram per day, paracetamol may marginally elevate systolic blood pressure in hypertensive patients. Although it’s uncertain whether paracetamol is the real reason of this increase, studies show that children of mothers who used paracetamol for an extended period of time during pregnancy had higher rates of asthma, developmental, and reproductive issues. A maximum of three to four grammes per day is advised for adults. Toxicity from higher doses, including liver failure, is a possibility. Most drug overdoses in the US, UK, Australia, and New Zealand are caused by paracetamol poisoning, which is the leading cause of acute liver failure in the Western world.

Expression and functions of transient receptor potential channels in liver diseases.

Liver diseases constitute a major healthcare burden globally, including acute hepatic injury resulted from acetaminophen overdose, ischemia-reperfusion or hepatotropic viral infection and chronic hepatitis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Attainable treatment strategies for most liver diseases remain inadequate, highlighting the importance of substantial pathogenesis. The transient receptor potential (TRP) channels represent a versatile signalling mechanism regulating fundamental physiological processes in the liver. It is not surprising that liver diseases become a newly explored field to enrich our knowledge of TRP channels. Here, we discuss recent findings revealing TRP functions across the fundamental pathological course from early hepatocellular injury caused by various insults, to inflammation, subsequent fibrosis and hepatoma. We also explore expression levels of TRPs in liver tissues of ALD, NAFLD and HCC patients from Gene Expression Omnibus (GEO) or The Cancer Genome Atlas (TCGA) database and survival analysis estimated by Kaplan-Meier Plotter. At last, we address the therapeutical potential and challenges by pharmacologically targeting TRPs to treat liver diseases. The aim is to provide a better understanding of the implications of TRP channels in liver diseases, contributing to the discovery of novel therapeutic targets and efficient drugs.

Quercetin and Resveratrol are Associated with the Downregulation of TNF-&amp;#945;/NF-kB/iNOS Axis-Mediated Acute Liver Injury in Rats Induced by Paracetamol Poisoning

Paracetamol (known as acetaminophen, or APAP) poisoning causes acute liver damage that can lead to organ failure and death. We sought to determine that APAP overdose can augment tumor necrosis factor-alpha (TNF-α)/ nuclear factor kappa B (NF-kB)/induced nitic oxide synthase (iNOS) axis-mediated hepatotoxicity in rats, and the anti-inflammatory polyphenolic compounds, quercetin (QUR) plus resveratrol (RES) can ameliorate these parameters. Therefore, we induced acute hepatotoxicity in rats using APAP overdose (2 g/kg, orally) and the protective group of rats were treated with 50 mg/kg QUR plus 30 mg/kg RES for one week before APAP ingestion. Animals were killed at day 8. APAP poisoning caused the induction of hepatic tissue levels of TNF-α, NF-kB, and iNOS, which were significantly (p<0.05) decreased by QUR+RES. QUR+RES, also inhibited liver injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, a link between liver injury and TNF-α /NF-kB / iNOS axis mediated hepatotoxicity was observed. Thus, the presented data backing the conclusion that intoxication by paracetamol increases TNF-α / NF-kB / iNOS axis -mediated hepatotoxicity, and is protected by a combination of quercetin and resveratrol.

Hepatoprotective Effect of Vitamin B12 in Acetaminophen Induce Hepatotoxicity in Male Rats.

Acetaminophen is a pharmaceutical synthesized non-opioid analgesic that belongs to the "aniline analgesics" class of medicine. Because it lacks a significant anti-inflammatory effect, it is not classified as a non-steroidal anti-inflammatory therapeutic medication (NSAID). As an over-the-counter pain reliever and antipyretic, Acetaminophen is the active metabolite of phenacetin and acetanilide, but it is less toxic than either precursor. According to some medical studies, Acetaminophen toxicity can be treated with vitamin B12. Acetaminophen-poisoned Male Wister rats were the subject model of the current study, which examines the effects of vitamin B12 on their hepatic health. There were three groups of animals: Acetaminophen treated animals (750 ml/kg), vitamin B12-treated animals (0.63 g/kg), and a control group that received distilled water (750 ml/kg). All animals were given oral medication for seven days. On the seventh day, the animal was sacrificed. Plasma levels of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Glutathione (GSH), total antioxidant capacity (TAC), Caspase3, Malondialdehyde (MDA), Interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-) were measured in the cardiac blood samples. Vitamin B12 lowers liver enzyme levels in the blood, increases overall antioxidant levels, and compensates for tissue glutathione deficiency while lowering serum elevations. TNF-α and interleukin-6 levels are also reduced by caspase3. Acetaminophen-induced hepatic necrosis and inflammatory cell infiltration were both considerably reduced by vitamin B12 supplementation. According to this study, vitamin B12 was found to have a protective effect against acetaminophen-induced hepatotoxicity.

Cathelicidin promotes liver repair after acetaminophen-induced liver injury in mice

Acetaminophen (APAP)-induced acute liver injury (AILI) is a leading cause of acute liver failure (ALF). N-acetylcysteine (NAC) is only effective within 24h after APAP intoxication, raising an urgent need for alternative approaches to treat this disease. This study aimed to test whether cathelicidin (Camp), which is a protective factor in chronic liver diseases, protects mice against APAP-induced liver injury and ALF. A clinically relevant AILI model and an APAP-induced ALF model were generated in mice. Genetic and pharmacological approaches were used to interfere with the levels of cathelicidin invivo. An increase in hepatic pro-CRAMP/CRAMP (the precursor and mature forms of mouse cathelicidin) was observed in APAP-intoxicated mice. Upregulated cathelicidin was derived from liver-infiltrating neutrophils. Compared with wild-type littermates, Camp knockout had no effect on hepatic injury but dampened hepatic repair in AILI and reduced survival in APAP-induced ALF. CRAMP administration reversed impaired liver recovery observed in APAP-challenged Camp knockout mice. Delayed CRAMP, CRAMP(1-39) (the extended form of CRAMP), or LL-37 (the mature form of human cathelicidin) treatment exhibited a therapeutic benefit for AILI. Co-treatment of cathelicidin and NAC in AILI displayed a stronger hepatoprotective effect than NAC alone. A similar additive effect of CRAMP(1-39)/LL-37 and NAC was observed in APAP-induced ALF. The pro-reparative role of cathelicidin in the APAP-damaged liver was attributed to an accelerated resolution of inflammation at the onset of liver repair, possibly through enhanced neutrophil phagocytosis of necrotic cell debris in an autocrine manner. Cathelicidin reduces APAP-induced liver injury and ALF in mice by promoting liver recovery via facilitating inflammation resolution, suggesting a therapeutic potential for late-presenting patients with AILI with or without ALF. Acetaminophen-induced acute liver injury is a leading cause of acute liver failure. The efficacy of N-acetylcysteine, the only clinically approved drug against acetaminophen-induced acute liver injury, is significantly reduced for late-presenting patients. We found that cathelicidin exhibits a great therapeutic potential in mice with acetaminophen-induced liver injury or acute liver failure, which makes up for the limitation of N-acetylcysteine therapy by specifically promoting liver repair after acetaminophen intoxication. The pro-reparative role of cathelicidin, as a key effector molecule of neutrophils, in the APAP-injured liver is attributed to an accelerated resolution of inflammation at the onset of liver repair, possibly through enhanced phagocytic function of neutrophils in an autocrine manner.

Procyanidins Ameliorate Acetaminophen-induced Acute Liver Injury via Activating the Nrf-2/SOD-1 Signal Pathway

Background and Objectives An overdose of acetaminophen (APAP) usually leads to acute liver injury, and oxidative stress is one of the fundamental mechanisms used to characterize it. Procyanidins (PCs) can reduce the oxidative stress in the liver of mice. This study aimed to investigate the potential protective role of PCs against APAP-induced acute liver injury. Materials and Methods Experiments were performed on male Kunming mice in six groups: phosphate-buffered saline, PCs, APAP, and PCs pretreated with 10, 50, and 100 mg/kg. The mice were peritoneally injected with PCs 30 min before the administration of APAP. First, survival rates of mice were scored every 12 hr for three days in succession. Furthermore, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (T-Bil), total cholesterol (TC), triglyceride (TG), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-1 (IL-6) were determined. Additionally, histological analysis and hepatic oxidative stress including the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) were assessed. Finally, the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and SOD-1 was detected by Western blotting. Results The data indicated that PCs improved survival rates of APAP-induced liver injury in mice models. Moreover, PCs could reduce the elevated serum levels of ALT, AST, T-Bil, TC, TG, TNF-α, IL-1β, and IL-6 due to APAP exposure with a dose-dependent manner. Besides, PCs pretreatment attenuated hepatic histopathological damage and oxidative stress which manifested the increases of SOD and GSH, whereas the decrease of MDA. Furthermore, PCs enhanced the protein expression of Nrf2 and SOD-1 in the PCs pretreatment groups compared with the APAP group. Conclusion PCs ameliorated APAP-induced acute liver injury, and Nrf2 signaling pathway modulating antioxidative stress might be involved in it.

Unveiling electrocatalytic performance of MnCo-P on sulfur-doped reduced graphene oxide for electrochemical detection of acetaminophen

It is well known that the overdose and prolonged use of acetaminophen (AAP) drugs could cause severe health issues for human beings. In order to prevent such health issues, it is important to electrochemically monitor the level of AAP in the human body and consumption sources such as river and lake water. In this study, we have developed an electrode modified with manganese cobalt phosphide (MnCo-P) onto sulfur-doped reduced graphene oxide (S-RGO) composite for electrochemical detection of AAP. The cyclic voltammetry analysis shows that the synergistic activity of MnCo-P and S-RGO in the MnCo-P/S-RGO composite obtained a high current responsibility towards the electrochemical detection of AAP. Further, the amperometry (i-t) analysis of MnCo-P/S-RGO for AAP demonstrated a low detection limit of 1.39 nM in the linear range of 0.05 to 1.94 µM and a sensitivity of 0.658 µA µM−1cm−2 which are appreciable. The real sample analysis recovery (%) from AAP detection in tablet, human urine, and river water samples indicates the MnCo-P/S-RGO modified electrode is significant for AAP level monitor in clinical.