We report a patient with glutathione synthetase (GS) deficiency who developed acetaminophen-induced hepatotoxicity after a two-day treatment with regular doses of acetaminophen. A nine-month-old female was referred because of intractable metabolic acidosis. She was given acetaminophen at therapeutic doses over a 48-hour period. She was hospitalized because of confusion and metabolic acidosis. L...

Purpose: Endogenous metabolic profiles have been shown to predict the fate and toxicity of drugs such as acetaminophen in healthy individuals. However, the clinical utility of metabonomics in oncology remains to be defined. We aimed to evaluate the effect of pretreatment serum metabolic profiles generated by H NMR spectroscopy on toxicity in patients with inoperable colorectal cancer receiving ...

Our objective was to identify microRNA (miRNA) biomarkers of drug-induced liver and kidney injury by profiling the circulating miRNome in patients with acetaminophen overdose. Plasma miRNAs were quantified in age- and sex-matched overdose patients with (N = 27) and without (N = 27) organ injury (APAP-TOX and APAP-no TOX, respectively). Classifier miRNAs were tested in a separate cohort (N = 81)...

BACKGROUND Recent case reports suggest that consumption of ethanol may increase the risk of liver injury induced by acetaminophen (INN, paracetamol). However, this possibility is at odds with previous clinical studies that showed that acute ethanol ingestion could protect against hepatotoxicity by inhibiting CYP-mediated acetaminophen oxidation. We tested the hypothesis that ethanol ingestion c...

The discipline of toxicology considers the adverse effects of chemicals, including drugs, and other agents, such as biological toxins and radiation, on biological systems. Toxicity associated with drug action can generally be characterized as either an extension of the therapeutic effect, such as the fatal central nervous system (CNS) depression that may follow a barbiturate overdose, or as an ...

In this study, we focus on a novel multi-scale modeling approach for spatiotemporal prediction of the distribution of substances and resulting hepatotoxicity by combining cellular models, a 2D liver model, and whole body model. As a case study, we focused on predicting human hepatotoxicity upon treatment with acetaminophen based on in vitro toxicity data and potential inter-individual variabili...

BACKGROUND Acetaminophen is a common antipyretic drug but at overdose can cause severe hepatotoxicity that may further develop into liver failure and hepatic centrilobular necrosis in experimental animals and humans. This study was undertaken to assess the ameliorative role of Moringa peregrina leaves extract against acetaminophen toxicity in rats. MATERIALS AND METHODS Induction of hepatotox...

It has been shown that hepatocytes cultured in a collagen sandwich configuration maintain cell viability, morphology, and drug metabolizing activities for several weeks. The purpose of this study was to characterize chemically induced general toxicity in this system by exposing hepatocytes to eight different hepatotoxic compounds. Cell function and viability was measured by analyzing the secret...

The aim of this study was to investigate the protective effects of phospholipase A2 (PLA2) from bee venom against acetaminophen-induced hepatotoxicity through CD4+CD25+Foxp3+ T cells (Treg) in mice. Acetaminophen (APAP) is a widely used antipyretic and analgesic, but an acute or cumulative overdose of acetaminophen can cause severe hepatic failure. Tregs have been reported to possess protective...