Acetaminophen Overdose Research Articles

Characteristic of Paracetamol Overdose Before and During COVID-19 Pandemic, Saudi Arabia, 2019-2020

Purpose: Paracetamol is the most used medication worldwide; due to its analgesic and antipyretic effect; it had been included within the recommended regimen for COVID-19 patients. This study aimed at exploring the changes in the incidence of paracetamol overdose during pandemic compared to pre-pandemic periods.
 Methodology: Through a record-based study, all cases of paracetamol overdose who had been reported to the ministry of health in Saudi Arabia in the period between January 2019 and December 2020 were included in the study. Data stored in electronic form were retrieved and analyzed using SPSS version 26. Frequency distribution was used to describe categorical variables.
 Findings: Two hundred and forty four paracetamol overdose cases were reported in 2020 (during the pandemic) compared to 449 in 2019 (pre-pandemic) with dominance of females (62.6%) and Saudis (86.7%). Most cases ingested paracetamol orally mainly in solid forms (76.5%), and they were mostly diagnosed as confirmed cases on admission (84.6%). The great majority recovered and discharged (87.8%). The overall annual incidence of paracetamol in (pre-pandemic) was 1.32/100,000 which dropped markedly during pandemic to 0.71/100,000.
 Conclusion: There was a general decline in the incidence of paracetamol overdose during COVID-19 pandemic, with relative increase in incidence in home incidents and in children.
 Recommendation: Health education to the public to increase their awareness about proper and safe use of paracetamol is highly recommended, as well as introducing instructions and guidelines for practitioners about prescribing it.

Antioxidant effect of Abelmoschus Esculentus against acetaminophen-induced nephrotoxicity: an experimental study

Acetaminophen(APAP) intoxication is an important cause of nephrotoxicity and hepatotoxicity. N-acetylcysteine(NAC) is used in the treatment, but it has some serious side effects. Abelmoschus esculentus(AE) has various benefits as well as antioxidant effects. This study aims to investigate the effect of AE in APAP-induced acute nephrotoxicity. Forty male Wistar rats were divided into five equal groups: Control, AE, APAP, APAP+AE, and APAP+AE+NAC. Significant changes were observed in serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), Neutrophil Gelatinase-Associated Lipocalin(NGAL) and Kidney Injury Molecule-1(KIM-1) after induction with APAP. NGAL and KIM-1 in the AE group remained low compared to those receiving APAP (p=0.022 and p0.001, respectively). When the APAP group was compared with the AE and AE+NAC groups, it was found that even the administration of AE alone significantly decreased NGAL and KIM-1(p=0.036 vs.p=0.029 and p0.001 vs. p0.001, respectively), these results were attributed to the effects of AE on reducing MDA and increasing SOD. Histopathological studies also confirmed these results. These results demonstrated that AE had protective and therapeutic effects on APAP-induced nephrotoxicity. This benefit of AE is due to its antioxidant effect. In addition, AE may also increase the regenerative capacity of the kidney, which APAP reduces.

First-in-human study to evaluate the safety, tolerability and pharmacokinetics of a novel analgesic and antipyretic drug with structural similarity to acetaminophen

JNJ-10450232 (NTM-006) is a new molecular entity that comprises structural similarities to acetaminophen and provides comparable analgesia in animals and humans without causing the hepatotoxicity associated with acetaminophen overdose in preclinical models. This double-blind, placebo-controlled, first-in-human study evaluated the safety, tolerability, and pharmacokinetics of JNJ-10450232 (NTM-006) following single (50–6000 mg) and multiple (250–2500 mg twice daily for 8 days) doses in healthy male volunteers. JNJ-10450232 (NTM-006) was absorbed within 1–3 h, except at high doses at which Cmax was delayed and bimodal, while increases in AUC were more than dose proportional. CL/F and Vd/F decreased approximately 3-fold with increasing single doses up to 6000 mg and multiple doses up to 1000 mg, resulting in similar t½ values that ranged from 8 to 10 h across doses. JNJ-10450232 (NTM-006) was generally safe and well tolerated, and no dose-limiting toxicities were observed. Transient increases in indirect bilirubin were noted at post-baseline timepoints due to UGT1A1 inhibition, without any evidence of adverse hepatic effects. Macular rash and generalized erythema were the most common drug-related adverse events after multiple doses.

Characterization and Quantification of Oxidized High Mobility Group Box 1 Proteoforms Secreted from Hepatocytes by Toxic Levels of Acetaminophen.

The high mobility group box 1 (HMGB1), which is released during acute acetaminophen (APAP) overdose, is thought to mediate a subsequent immune response, particularly hepatic infiltration of macrophages. The redox behavior of HMGB1 and the proteoforms of HMGB1 present in oxidative environments has been the subject of a number of confusing and contradictory studies. Therefore, a stable isotope dilution two-dimensional nanoultrahigh-performance liquid chromatography parallel reaction monitoring/high-resolution mass spectrometry method was developed in order to characterize and quantify oxidative modifications to the cysteine (Cys) residues (Cys-23, Cys-45, and Cys-106) that are present in HMGB1. Disulfide linkages were determined using carbamidoethyl derivatization before and after reduction as well as by direct analysis of disulfide cross-linked peptides. A stable isotope labeled form of HMGB1 was used as an internal standard to correct for sample to sample differences in immunoaffinity precipitation, derivatization, and electrospray ionization. Four discrete HMGB1 proteoforms were found to be released from a hepatocarcinoma cell model of APAP overdose after 24 h. Fully reduced HMGB1 with all three Cys-residues in their free thiol state accounted for 18% of the secreted HMGB1. The proteoform with disulfide between Cys-23 and Cys-45 accounted for 24% of the HMGB1. No evidence was obtained for a disulfide cross-link between Cys-106 and the other two Cys-residues. However, 45% of the HMGB1 formed a cross-link with unidentified intracellular proteins via an intermolecular disulfide bond, and 12% was present as the terminally oxidized cysteic acid. Surprisingly, there was no evidence for the formation of HMGB1 disulfides with GSH or other low molecular weight thiols. Secreted plasma HMGB1 Cys-23/Cys45 disulfide proteoform together with the Cys-106/protein disulfide proteoforms could potentially serve as early biomarkers of hepatoxicity after APAP overdose as well as biomarkers of drug-induced liver injury.

Nicotinamide adenine dinucleotide attenuates acetaminophen-induced acute liver injury via activation of PARP1, Sirt1, and Nrf2 in mice.

The aim of this study was to investigate the protective effect of nicotinamide adenine dinucleotide (NAD+) against acute liver injury (ALI) induced by acetaminophen (APAP) overdose in mice. First, serum transaminases were used to assess the protective effect of NAD+, and the data revealed that NAD+ mitigated the APAP-induced ALI in a dose-dependent manner. Then, we performed hematoxylin-eosin staining of liver tissues and found that NAD+ alleviated the abnormalities of histopathology. Meanwhile, increase in the malondialdehyde content and decrease in glutathione, superoxide dismutase (SOD), and glutathione peroxidase were identified in the APAP group, which were partially prevented by the NAD+ pretreatment. Moreover, compared with the mice treated with APAP only, the expression of poly ADP-ribose polymerase 1 (PARP1), Sirtuin1 (Sirt1), SOD2, nuclear factor erythroid 2-related factor 2 (Nrf2), and hemoxygenase-1 was upregulated, while Kelch-like ECH-associated protein 1 and histone H2AX phosphorylated on Ser-139 were downregulated by NAD+ in NAD+ + APAP group. Conversely, NAD+ could not correct the elevated expression of phospho-Jun N-terminal kinase and phospho-extracellular signal-regulated kinase induced by APAP. Taken together, these findings suggest that NAD+ confers an anti-ALI effect to enhance the expression of PARP1 and Sirt1, and to simultaneously stimulate the Nrf2 anti-oxidant signaling pathway.

Management of Acute Liver Failure: Update 2022.

Abbreviated pathogenesis and clinical course of the acute liver failure syndrome. The pathogenesis and clinical course of the syndrome of acute liver failure (ALF) differs depending upon the etiology of the primary liver injury. In turn, the severity of the liver injury and resulting synthetic failure is often the primary determinant of whether a patient is referred for emergency liver transplantation. Injuries by viral etiologies trigger the innate immune system via pathogen-associated molecular patterns (PAMPs), while toxin-induced (and presumably ischemia-induced) injuries do so via damage-associated molecular patterns (DAMPs). The course of the clinical syndrome further depends upon the relative intensity and composition of cytokine release, resulting in an early proinflammatory phenotype (SIRS) and later compensatory anti-inflammatory response phenotype (CARS). The outcomes of overwhelming immune activation are the systemic (extrahepatic) features of ALF (cardiovascular collapse, cerebral edema, acute kidney injury, respiratory failure, sepsis) which ultimately determine the likelihood of death.Acute liver failure (ALF) continues to carry a high risk of mortality or the need for transplantation despite recent improvements in overall outcomes over the past two decades. Optimal management begins with identifying that liver failure is indeed present and its etiology, since outcomes and the need for transplantation vary widely across the different etiologies. Most causes of ALF can be divided into hyperacute (ischemia and acetaminophen) and subacute types (other etiologies), based on time of evolution of signs and symptoms of liver failure; the former evolve in 3 to 4 days and the latter typically in 2 to 4 weeks. Both involve intense release of cytokines and hepatocellular contents into the circulation with multiorgan effects/consequences.Management involves optimizing fluid balance and cardiovascular support, including the use of continuous renal replacement therapy, vasopressors, and pulmonary ventilation. Early evaluation for liver transplantation is advised particularly for acetaminophen toxicity, which evolves so rapidly that delay is likely to lead to death.Vasopressor support, high-grade hepatic encephalopathy, and unfavorable (subacute) etiologies heighten the need for urgent listing for liver transplantation. Prognostic scores such as Kings Criteria, Model for End-Stage Liver Disease, and the Acute Liver Failure Group prognostic index take these features into account and provide reasonable but imperfect predictive accuracy. Future treatments may include liver support devices and/or agents that improve hepatocyte regeneration.

Drug-Induced Hepatitis in Children: The Experience of a Single Center in Romania.

Drug-induced liver injury (DILI) is uncommon but potentially lethal. Over 6 years, 2533 children with acute liver disease were identified in our center, 48 of which suffered from toxic hepatitis, and 40 exhibited DILI (22 paracetamol-related, 14 albendazole-related). The most affected children were in the 13–17-year-old age group. The mean time between drug ingestion and disease diagnosis was 25.4 h for paracetamol-related DILI and 21.6 days for the albendazole-related group. Clinical features were mostly gastrointestinal, jaundice being reported in 30% of the cases. Regarding the type of liver injury, for 70% of the patients it was hepatocellular (mostly paracetamol toxicity), for 11% cholestatic, and for 19% mixed (albendazole-related). The mean initial ALT value was 1020 U/L for all DILIs. Coagulopathy was only identified for the acetaminophen-related group. The median number of hospitalization days was 6.9 for DILI related to acetaminophen ingestion, compared with 7 for the idiosyncratic pattern. When applying the DILI severity index, 81% of the patients were categorized as having a mild hepatic ailment, while 19% had a moderate–severe or severe disease. No deaths were reported in the study group. The diagnosis of DILI involves the exclusion of other causes of liver injury; therefore, it is considered one of the most challenging diagnoses in hepatology.

Generation of pro-and anti-inflammatory mediators after acetaminophen overdose in surviving and non-surviving patients

Acetaminophen (APAP) overdose causes liver injury in animals and humans. Although well-studied in animals, limited longitudinal data exist on cytokine release after APAP overdose in patients. The purpose of this study was to quantify concentrations of cytokines in APAP overdose patients to determine if early cytokine or complement measurements can distinguish between surviving and non-surviving patients. Plasma was obtained from healthy controls, APAP overdose patients with no increase in liver transaminases, and surviving and non-surviving APAP overdose patients with severe liver injury. Interleukin-10 (IL-10), and CC chemokine ligand-2 (CCL2, MCP-1) were substantially elevated in surviving and non-surviving patients, whereas IL-6 and CXC chemokine ligand-8 (CXCL8, IL-8) had early elevations in a subset of patients only with liver injury. Day 1 IL-10 and IL-6 levels, and Day 2 CCL2, levels correlated positively with survival. There was no significant increase in IL-1α, IL-1β or TNF-α in any patient during the first week after APAP. Monitoring cytokines such as CCL2 may be a good indicator of patient prognosis; furthermore, these data indicate the inflammatory response after APAP overdose in patients is not mediated by a second phase of inflammation driven by the inflammasome.

Antioxidant Mechanism of Renal and Hepatic Failure Prevention Related to Paracetamol Overdose by the Aqueous Extract of Amblygonocarpus andongensis Stem Bark.

Paracetamol is a commonly used analgesic/antipyretic whose long-term intake or overdose is associated with renal and hepatic injuries. The aim of this study was to determine the hepatonephroprotective mechanisms of the aqueous extract of Amblygonocarpus andongensis stem bark (AEAASB) on renal and hepatic failure resulting from paracetamol overdose. Forty-five rats were divided into nine groups (n = 5); these were treated once daily for 8 days with 5 ml/kg distilled water (normal, negative, and satellite controls); 0.9% normal saline and 140 mg/kg N-acetyl-cysteine (positive controls); 125, 250, and 500 mg/kg AEAASB (test groups); and 500 mg/kg AEAASB (satellite test). On day 8 after different treatments, hepatonephrotoxicity was induced in all the groups except the normal group by oral administration of a single dose of paracetamol (1000 mg/kg). Urinary, hematological, serum, and oxidative stress parameters and in vitro antioxidant activity of AEAASB were evaluated. Histological sections of the liver and kidney were performed. AEAASB significantly decreased urea, creatinine, transaminases, alkaline phosphatase, and bilirubin (p < 0.001) at 500 mg/kg compared to the negative control. Significant decreases in hepatic (p < 0.01) and renal (p < 0.001) malondialdehyde levels were associated with increases in superoxide dismutase, catalase, and reduced glutathione levels in 500 mg/kg AEAASB compared with the negative control. Histological analysis showed that AEAASB prevented paracetamol-induced renal and liver tissue damage. Furthermore, AEAASB revealed a very strong antioxidant activity (inhibitory concentration 50 = 180 μg/ml, antioxidant activity index = 5.55) with an ability to scavenge 63.03% 2,2-diphenyl-2-picrylhy-drazyl radical and reduced ferric iron by 52.68 mgEqVitC/100 g DM. The hepatonephroprotective effect of AEAASB might result from its ability to improve the antioxidant status through the stimulation of antioxidant factors and the scavenging of free radicals. This property could be ascribed to the presence of some classes of bioactive compounds such as phenolic compounds in great amounts.

Sarmentosin promotes USP17 and regulates Nrf2-mediated mitophagy and cellular oxidative stress to alleviate APAP-induced acute liver failure

BackgroundAn overdose of acetaminophen (APAP), the main cause of acute liver failure (ALF), induces oxidative stress that ultimately causes mitochondrial impairment and hepatotoxicity. The nuclear factor erythroid 2-related factor 2 (Nrf2) was widely recognized as an anti-oxidative stress mechanism. The present study was aimed at investigating whether sarmentosin, extract from traditional Chinese medicine, protects the liver against APAP-induced injury via activating Nrf2 and subsequently decreasing oxidative stress. MethodsMale ICR mice were treated with sarmentosin oral administration for 1 week and injected APAP (300 mg/kg. i.p.) for acute liver injury model. The liver and serum of mice for histological and biochemistry analysis. AML12 and LO2 cells were used in vitro assays. ResultsWe found that sarmentosin moderately increased accumulation of Nrf2 via upregulating USP17-mediated ubiquitin inhibition at the early stage of hepatocytes damage. The Nrf2 separating from bonding protein Keap1 translocated into nucleus and activated downstream gene of antioxidants. Mitophagy, a unique autophagy can remove Reactive Oxygen Species (ROS) damaged mitochondria, was elevated in this progress to maintain mitochondria function and ROS homeostasis. ConclusionIn summary, our research revealed that sarmentosin could alleviate APAP-induced liver acute injury through USP17-mediated Nrf2 overexpression and PINK1-dependent mitophagy.

Platanosides, a Potential Botanical Drug Combination, Decrease Liver Injury Caused by Acetaminophen Overdose in Mice.

Oxidative stress plays an important role in acetaminophen (APAP)-induced hepatotoxicity. Platanosides (PTSs) isolated from the American sycamore tree (Platanus occidentalis) represent a potential new four-molecule botanical drug class of antibiotics active against drug-resistant infectious disease. Preliminary studies have suggested that PTSs are safe and well tolerated and have antioxidant properties. The potential utility of PTSs in decreasing APAP hepatotoxicity in mice in addition to an assessment of their potential with APAP for the control of infectious diseases along with pain and pyrexia associated with a bacterial infection was investigated. On PTS treatment in mice, serum alanine aminotransferase (ALT) release, hepatic centrilobular necrosis, and 4-hydroxynonenal (4-HNE) were markedly decreased. In addition, inducible nitric oxide synthase (iNOS) expression and c-Jun-N-terminal kinase (JNK) activation decreased when mice overdosed with APAP were treated with PTSs. Computational studies suggested that PTSs may act as JNK-1/2 and Keap1-Nrf2 inhibitors and that the isomeric mixture could provide greater efficacy than the individual molecules. Overall, PTSs represent promising botanical drugs for hepatoprotection and drug-resistant bacterial infections and are effective in protecting against APAP-related hepatotoxicity, which decreases liver necrosis and inflammation, iNOS expression, and oxidative and nitrative stresses, possibly by preventing persistent JNK activation.

Polysaccharide from Echinacea purpurea plant ameliorates oxidative stress-induced liver injury by promoting Parkin-dependent autophagy

Background: Acetaminophen (APAP) overdose represents one of the most common drug-induced liver injuries (DILI) worldwide. Oxidative damage to the hepatocytes and their resultant autophagy are the key components in the APAP-induced DILI. Echinacea purpurea polysaccharide (EPPS), the component extracted from the root of Echinacea purpurea (L.) Moench, shows various biological functions including immunoregulation and antioxidant activity.Purpose: This study aimed to elucidate the protective effect of EPPS against APAP-induced DILI and the underlying mechanisms. Results: EPPS attenuates APAP overdose induced DILI in mice and ameliorates inflammation and oxidative stress in mice with APAP overdose-induced DILI. Furthermore, EPPS protected the hepatocytes against APAP-induced liver injury by suppressing apoptosis. EPPS ameliorates APAP-induced DILI via an autophagy-dependent mechanism in vivo and increases autophagy with a reduction in oxidative stress and inflammation in vitro. Parkin knockdown prevents the autophagic-dependent manner of EPPS effects in APAP-treated hepatocytes.Conclusions: EPPS exhibited a strong hepatoprotective effect against APAP-induced DILI and was correlated with reduction of autophagy-dependent oxidant response, inflammation, and apoptosis. Moreover, the findings indicated that EPPS exerts its hepatoprotective effect against APAP mainly via Parkin-dependent autophagy, and the use of EPPS can serve as a promising novel therapeutic strategy for APAP-induced DILI.

Clinical Profile and Outcomes of Poisonings and Drug Overdose at King Saud Medical City

Introduction: Poisoning is a critical worldwide problem, having been reported in countries across the continent [1]. A significant number of emergency room visits are due to poisonings and drug overdose. Poisonings is a major cause of the increase in morbidity and mortality [2] of adults. Ingestion of different poisons can intentional or accidental. Poisoning can occur following ingestion, inhalational, or sometimes snuffing of drugs. Regardless of the method of poisoning , it usually leads to catastrophic outcomes. Study population:Any patient aged more than 15 years, who presented to the Emergency Department (ED) of King Saud Medical City (KSMC). Riyadh, Saudi Arabia, with a drug overdose, chemical ingestion/inhalation,poisoning or alcohol intoxication was recruited for this study. Methods: A study of all the patients that presented to our hospital from the period of January 2020 until September, 2020 was recruited for this horizontal study. Initial data was collected manually. An online Excel sheet was created, and the following parameters were collected; age, gender, and nationality, information regarding the ingested/inhaled substance, patients’ signs, and symptoms upon presentation to the Emergency room, and various laboratory tests.Patients were followed till they were in the hospital and finally disposed. Statistical analysis was then performed on the collected data. Results:Most of the patients (65.7%) were males. (69.4 %) were Saudi nationals with a mean age of 33-years. The most common presenting symptom is decreased level of consciousness (35 cases). Paracetamol overdose accounted for 12% of the cases, alcohol accounted for 10.2%. More than 50% of our patients had mixed drug poisoning or unidentifiable poison. The maximum reading for blood pressure was 221/149 mmHg among the benzodiazepine overdose group. The respiratory rate was within the normal limit in all patients.Mortaliyu was below 1%. Conclusion: Drug overdose is a common cause of emergency room visits and hospital admission. Paracetamol was the commonest cause of identifiable drug overdose, followed by Alcohol ingestion. But mixed poisoning involving mutiple drugs were quite common these days. Outcome was generally good with just less than 1% mortality.

A jojoba (Simmondsia chinensis) seed cake extracts express hepatoprotective activity against paracetamol-induced toxicity in rats

This study aimed to investigate the hepatoprotective activity of jojoba seed cake extracts against an acute paracetamol (PC) intoxication. Two aqueous extracts from jojoba (Simmondsia chinensis) seed cake, a simmondsin-rich extract (WE), and a simmondsin-hydrolyzed extract (NE) using Viscozyme L enzyme have been prepared and characterized. After enzyme treatment, simmondsin content decreased from 33.0 % to 3.0 % and glucose content increased from 16.2 % to 27.3 % reflecting simmondsin hydrolysis. Both extracts were administered to different rat groups via gavage (0.6 g/kg b.w.) before PC treatment (2 g/kg b.w.) three times a week for 3 weeks. The PC intoxication altered the serum biomarkers, the oxidative status, and the Tumor necrosis factor alpha (TNF-α), Bax and Bcl-2 protein expressions of tested animals. In addition, the histological analysis of liver tissues proved significant injury and hepatocellular necrosis. WE and NE extract showed a relatively high in vitro radical scavenging (ORAC) and averting activities (HORAC) with a polyphenol content of 3.6 % and 2.9 %, respectively. Both extracts showed a powerful in vivo hepatoprotective activity against PC-induced toxicity by improving the hepatocellular antioxidant status and blocking proteins expression (TNF-α, Bax and Bcl-2), involved in inflammation and liver damage. However, the enzymatic treatment improved the hepatoprotective activity of NE despite its lower simmondsin content and lower in vitro antioxidant capacity. This enhancement could be linked to the synergetic effect between the antioxidant components and the new hydrolytic products as glucose, uronic acids, arabinose and simmondsin-aglycons. These results suggest that jojoba waste could be potentially valorized in developing hepatoprotective drugs.

Paracetamol Overdose Induces Acute Liver Injury accompanied by oxidative stress and inflammation

Paracetamol Overdose Induces Acute Liver Injury accompanied by oxidative stress and inflammation

Acetaminophen Hepatotoxicity: Not as Simple as One Might Think! Introductory Comments on the Special Issue-Recent Advances in Acetaminophen Hepatotoxicity.

Acetaminophen (N-acetyl-para-aminophenol (APAP)) is one of the most-studied drugs worldwide [...]

Acute Liver Failure.

Acute liver failure (ALF) is a rare but life-threatening disease process that can result in rapidly progressive encephalopathy, elevated intracranial pressure, and multiorgan failure. In the United States, the 2 most common causes of ALF in the intensive care unit (ICU) are acetaminophen overdose and hypoxic-ischemic hepatopathy. Less common causes of ALF include alcoholic hepatitis, nonacetaminophen drug-induced liver injury, acute viral hepatitis, Wilson's disease, autoimmune hepatitis, and acute fatty liver of pregnancy. Unfortunately, there are many cases in which the cause of liver failure is indeterminate. ALF is an ICU emergency that requires close monitoring, extensive workup to determine etiology, frequent support of hemodynamic, respiratory, and renal function, administration of targeted therapies depending on the cause, utilization of N-acetylcysteine if appropriate, and consideration for liver transplant in select cases. The primary objective of this article is to define, diagnose, and detail the management of ALF in an ICU setting.

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

Many hospitals across the UK have instituted the modified 12-hour Scottish and Newcastle Anti-emetic Protocol (SNAP) for paracetamol poisoning but, to our knowledge, no validation has been undertaken of the SNAP for its perceived benefit of decreased length of stay (LoS). While the SNAP

FRI013 - Human paracetamol hepatotoxicity is mitigated by the gut-liver axis in vitro

FRI013 - Human paracetamol hepatotoxicity is mitigated by the gut-liver axis in vitro

Paracetamol Poisoning: Need to Remember Nephrotoxicity

Paracetamol overdose is an important cause of drug toxicity and pediatric overdose emergencies remain a significant global issue. Paracetamol is a known toxin to several tissues, but extrahepatic manifestations are not so well established as hepatotoxicity. Acute kidney injury occurs in up to 2% of paracetamol overdoses, generally coexisting with hepatotoxicity.