Possible Fatal Acetaminophen Intoxication with Atypical Clinical Presentation

De-Giorgio, Fabio; Lodise, Maria; Chiarotti, Marcello; d’Aloja, Ernesto; Carbone, Arnaldo; Valerio, Luca

doi:10.1111/1556-4029.12205

Cited by 13 publications

(11 citation statements)

References 16 publications

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“…High-dose APAP-induced clinical intoxication is predominantly found in liver and renal cells; therefore, the majority of previous studies have focussed on the mechanisms underlying high-dose APAP-triggered liver and renal injury ( 17 , 37 , 38 ). Furthermore, certain studies have indicated that APAP can exhibit antitumor activities in certain tumor types, including breast cancer, liver cancer and neuroblastoma ( 26 , 39 – 43 ).…”

Section: Introductionmentioning

confidence: 99%

Acetaminophen induces JNK/p38 signaling and activates the caspase-9-3-dependent cell death pathway in human mesenchymal stem cells

Yiang

Lin

et al. 2015

International Journal of Molecular Medicine

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Acetaminophen (APAP) is a widely used analgesic and antipyretic drug. Generally, the therapeutic dose of APAP is clinically safe, however, high doses of APAP can cause acute liver and kidney injury. Therefore, the majority of previous studies have focussed on elucidating the mechanisms of APAP-induced hepatotoxicity and nephrotoxicity, in addition to examining ways to treat these conditions in clinical cases. However, few studies have reported APAP-induced intoxication in human stem cells. Stem cells are important in cell proliferation, differentiation and repair during human development, particularly during fetal and child development. At present, whether APAP causes cytotoxic effects in human stem cells remains to be elucidated, therefore, the present study aimed to investigate the cellular effects of APAP treatment in human stem cells. The results of the present study revealed that high-dose APAP induced more marked cytotoxic effects in human mesenchymal stem cells (hMSCs) than in renal tubular cells. In addition, increased levels of hydrogen peroxide (H2O2), phosphorylation of c-Jun N-terminal kinase and p38, and activation of caspase-9/-3 cascade were observed in the APAP-treated hMSCs. By contrast, antioxidants, including vitamin C reduced APAP-induced augmentations in H2O2 levels, but did not inhibit the APAP-induced cytotoxic effects in the hMSCs. These results suggested that high doses of APAP may cause serious damage towards hMSCs.

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Section: Introductionmentioning

confidence: 99%

Acetaminophen induces JNK/p38 signaling and activates the caspase-9-3-dependent cell death pathway in human mesenchymal stem cells

Yiang

Lin

et al. 2015

International Journal of Molecular Medicine

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“…Among all patients with APAP intoxication, the prevalence rate of APAP-related renal function impairment has been estimated at <2% of all patients. 6 Most cases (53%) coexist with hepatic failure and acute kidney injury (AKI). Other cases of renal toxicity have mild liver involvement or no hepatic toxicity features.…”

Section: Introductionmentioning

confidence: 99%

Risk of Acute Kidney Injury and Long-Term Outcome in Patients With Acetaminophen Intoxication

et al. 2015

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Acetaminophen (APAP) intoxication is a common cause of hepatic toxicity and life-threatening hepatic failure. However, few studies have investigated the possible association between APAP intoxication and acute kidney injury (AKI). We constructed a retrospective cohort study to clarify the relationship between APAP intoxication and the risk of AKI.We identified patients with APAP intoxication and selected a comparison cohort that was 1:4 frequency matched according to age, sex, and year of APAP intoxication diagnosis from the Taiwan National Health Insurance Research Database from 1998 to 2010. We analyzed the risks of AKI for patients with APAP intoxication by using Cox proportional hazards regression models.In this study, 2914 patients with APAP intoxication and 11,656 controls were included. The overall risks of developing AKI were 2.41-fold in the patients with APAP intoxication compared with the comparison cohort. After we excluded APAP intoxication patients with coexisting AKI and hepatic failure/hepatitis, the overall risks of developing AKI were still 2.22-fold in the patients with APAP intoxication. There were 2 patients who had end-stage renal disease (ESRD) following APAP intoxication-related AKI. Limitations include retrospective review, selection bias, and absence of data on detail medications used, laboratory investigations and dosage of APAP intoxication.Our long-term cohort study results showed that AKI is a possible adverse effect among patients with APAP intoxication, regardless of whether patients have presented with hepatic toxicity. However, additional studies are necessary to clarify whether such patients can progress to ESRD.

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“…While paracetamol is described as relatively nontoxic in therapeutic doses, it can be toxic when taken in a single or repeated high dose, or after chronic ingestion. Adverse effects typically associated with paracetamol intoxication are include acute liver failure, renal tubular necrosis and hypoglycemic coma (De Giorgio et al, 2013, Lancaster et al, 2015. According to recent information provided by the American National Poison Data System (NPDS), paracetamol is one of the 25 drugs associated with the largest number of fatalities, either alone or in combination with other medications (Mowry et al, 2015).…”

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confidence: 99%

Effects of Aqueous Leaf Extract of Cashew Anacardium Occidentale on Paracetamol Induced Hepatotoxicity of Adult Male Wistar Rats

Okonkwo¹,

V.N.²,

Edeh³

2018

IJTSRD

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While paracetamol is described as relatively nontoxic when administered in therapeutic doses, it is known to cause toxicity when taken in a single or repeated high dose, or after chronic ingestion. Adverse events typically associated with paracetamol intoxication include acute liver failure (ALF), centrilobular hepatic necrosis, renal tubular necrosis and hypoglycemic coma. Cashew (Anacardium occidentale) has been used both as source of nutrition and medicinally worldwide. A total of 25 adult male Wistar rats weighing 100g-200g were used for this study. The animals were divided into 5 groups of 5 rats each. 1000mg/kg/body weight of paracetamol was given for 3 days to induce liver damage in groups BE. Group A served as the normal control group and received feed and water throughout the period of the experiment. Group B served as negative control group and received feeds and water throughout the period of the experiment, but no treatment with the extract. Group C, D and E received 150mg, 300mg and 500mg/kg of the extract for 21 days. All data obtained were subjected to statistical analysis using t-test, one-way ANOVA and POST HOC LSD using SPSS version 20. Differences between means were regarded significant at P<0.05. Data were expressed as mean + standard error of mean (SEM). The result showed a significant increase in AST in Group E (P<0.05) when compared to Group A. However, there was a decrease in Group C when compared to Group B. Also, there was a significant increase in ALT in Group D (P<0.05) and Group E (P<0.05), when compared to Group A. However, there was a decrease in Group C for both AST and ALT when compared to Group B. From this study, it can be said that aqueous leaf extract of Anacardium occidentale has a little correction effect on Paracetamol induced hepatotoxicity in small doses. However, it can exert a serious toxic effect on the liver with increased dosage. 1.1 BACKGROUND OF STUDY Paracetamol, also known as acetaminophen, is the most commonly used antipyretic and pain reliever and since 1955 has been available over-the-counter as a

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Possible Fatal Acetaminophen Intoxication with Atypical Clinical Presentation

Cited by 13 publications

References 16 publications

Acetaminophen induces JNK/p38 signaling and activates the caspase-9-3-dependent cell death pathway in human mesenchymal stem cells

Acetaminophen induces JNK/p38 signaling and activates the caspase-9-3-dependent cell death pathway in human mesenchymal stem cells

Risk of Acute Kidney Injury and Long-Term Outcome in Patients With Acetaminophen Intoxication

Effects of Aqueous Leaf Extract of Cashew Anacardium Occidentale on Paracetamol Induced Hepatotoxicity of Adult Male Wistar Rats

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