There is considerable evidence that the concentration of reduced gluthione in the liver is an important determinant of susceptibility to acetaminophen-induced hepatotoxicity. The role which different genetically determined levels of hepatic glutathione ma...

... toxic agents such as acetaminophen, the calcium lonophore A23187, or ... acetaminophen is dependent upon extensive metabolic activation, is ...

Acetaminophen can produce potentially fatal liver necrosis, via an intermediate toxic metabolite. Hepatic injury usually requires acute ingestion of at least 10-15 g of the drug. The patient typically feels well for one to three days before evidence of liver damage appears. Striking elevation of aminotransferases is characteristic, ...

... complete spelling of acetaminophen and all other active ingredients on the ... and wording on pharmacy container labels consistent with plain language and health ...

... toxicity; development of N-acetylcysteine (NAC) Page 5. APAP Protein ... transaminase values in serum � Treatment of mice with NAC reduced ...

In this case, a college student gives her cat Tylenol????? not knowing its potential harmful effects. The cat survives, but the incident motivates her to research the reaction mechanism underlying the liver toxicity of acetaminophen. The case outlines possible reaction schemes that would explain why acetaminophen-containing products ...

The toxicity of acetaminophen in freshly isolated hamster hepatocytes was investigated. Cells exposed to 2.5 mM acetaminophen for 90 min, followed by washing to completely remove unbound acetaminophen, and resuspension in fresh buffer, showed a dramatic decrease in viability over the ensuing 4.5 hr by which time ...

Male Wistar rats were dosed daily by gavage for 200 days with either (1) aspirin, 200 mg/kg; (2) acetaminophen, 200 mg/kg; (3) aspirin and acetaminophen, 200 mg/kg of each; (4) aspirin and acetaminophen, 100 mg/kg of each or (5) vehicle alone. None of the treatments produced any marked signs of toxicity and no drug ...

The research investigates the toxicity of the aspirin substitutes acetaminophen, phenacetin, and salicylamide. Fatalities, particularly in children, occur at relatively low doses of acetaminophen, due principally to hepatic necrosis, and also at relativel...

NON-IMMUNE MECHANISMS OF DILI: LESSONS FROM THE ACETAMINOPHEN MOUSE MODEL Neil Kaplowitz, MD ... Effect of JNK1+2 Knockdown (antisense) on Acetaminophen Toxicity 0 ...

Assesses the generality and strength of nonclinical youths' (N=569) perceptions of the harmfulness and lethality of acetaminophen in overdose. Findings indicate that adolescents have ready access to acetaminophen and use it in suicide attempts but underestimate its potential for toxicity, lacking knowledge regarding side effects of ...

... these medicines; formatting and wording on pharmacy container labels consistent with plain language and health literacy principles; a ...

With increasing frequency, the physician is confronted with the problem of determining the risk of liver toxicity in a person who may have ingested an overdose of acetaminophen. To be effective, antidotal therapy must be given early after acetaminophen ingestion when the patient, despite the toxic injury occurring ...

A reactive metabolite of acetaminophen is hepatotoxic in humans when the drug is ingested in large overdoses. The ability of the human fetal and adult liver to oxidize acetaminophen by trapping the potentially toxic metabolite as a glutathione conjugate has been measured. Oxidation by fetal liver was approximately ten times slower than ...

URLs Although acetaminophen (para- cetamol) has been used clinically for more than a century, its and colleagues have now provided evidence for a new and unexpected mechanism through which acetaminophen could exert its analgesic effects. Acetaminophen differs signifi- cantly from aspirin and other non- steroidal

... Pretreatment with prostaglandin synthesis inhibitors, indomethacin, acetylsalicylic acid and acetaminophen, increased the latency of the fever ...

clinically relevant levels of glucose, urea, ethanol, and acetaminophen in simulated human sera, in which of human serum. Glucose and urea are important metabolites. Ethanol and acetaminophen are potentially toxic. The concentra- tion range of ethanol and acetaminophen covered their toxic ...

... C. Hurley, and L. Clark. 2001. Use of acetaminophen for large scale control of brown treesnakes. Journal ... 2010.Richard E. Mauldin, Peter J. Savarie. (2010) Acetaminophen as an oral toxicant for Nile m...

Schultz et al (2008) raised the question whether regression into autism is triggered, not by the measles-mumps-rubella (MMR) vaccine, but by acetaminophen (Tylenol) given for its fever and pain. Considerable evidence supports this contention, most notably the exponential rise in the incidence of autism since 1980, when acetaminophen ...

There is a significant need to evaluate the therapeutic potential of natural products and other compounds purported to be hepatoprotective. Acetaminophen-induced liver injury, especially in mice, is an attractive and widely used model for this purpose because it is both clinically relevant and experimentally convenient. However, the pathophysiology of liver injury after ...

Hypoxia inducible factor (HIF) controls the transcription of genes involved in angiogenesis, erythropoiesis, glycolysis, and cell survival. HIF-1{alpha} levels are a critical determinant of HIF activity. The induction of HIF-1{alpha} was examined in the livers of mice treated with a toxic dose of APAP (300 mg/kg IP) and sacrificed at 1, 2, 4, 8, and 12 h. HIF-1{alpha} was ...

Acetaminophen/paracetamol-induced liver failure-which is induced by the binding of reactive metabolites to mitochondrial proteins and their disruption-is exacerbated by fasting. As fasting promotes SIRT3-mediated mitochondrial-protein deacetylation and acetaminophen metabolites bind to lysine residues, we investigated whether deacetylation predisposes mice ...

Inhibition of the cytochrome P-450-dependent formation of the acetaminophen-reactive metabolite was investigated as a possible mechanism for cysteamine protection against acetaminophen hepatotoxicity. Studies in isolated hamster hepatocytes indicated that cysteamine competitively inhibited the cytochrome P-450 enzyme system as represented by formation of ...

BackgroundAcetaminophen-cysteine adducts (APAP-CYS) are a specific biomarker of acetaminophen exposure. APAP-CYS concentrations have been described in the setting of acute overdose, and a concentration >1.1 nmol/ml has been suggested as a marker of hepatic injury from acetaminophen overdose in patients with an ALT >1000 IU/L. ...

The nuclear receptor, farnesoid X receptor (FXR, NR1H4), is known to regulate cholesterol, bile acid, lipoprotein, and glucose metabolism. In the current study, we provide evidence to support a role for FXR in hepatoprotection from acetaminophen (APAP)-induced toxicity. Pharmacological activation of FXR induces the expression of ...

PURPOSE: The present study examines the relationship between the dose of acetaminophen reported to have been ingested by patients and the occurrence of serum acetaminophen levels above the 'possible toxicity' line in patients presenting at the hospital after acetaminophen overdose. The prognostic value of ...

Acetaminophen, a pain-reliever, is one of the most widely used medications in the world. Acetaminophen with normal dosage is considered a nontoxic drug for therapeutic applications, but when taken at overdose levels it produces liver damage in human and various animal species. By a high energy mechanically activated method, we produced ...

... analysis suggests that 50% are related to drug hepatotoxicity (acetaminophen toxicity in 32%) and Page 5. 5 ... 2 x ULN in Alkaline Phosphate OR >2 ...

should avoid alcohol and any substances that are toxic to the liver, including acetaminophen (Tylenol). Fatty foods may cause vomiting, because substances from the liver are...

... The Toxic Exposure Surveillance System (TESS), now named the National Poison Data System (NPDS), which captures ... Brand Name, Generic Name, Dosage Form, Strength. ...

(Prognosis) Codeine is usually found in combination with other medications such as acetaminophen. Therefore outcome also depends on how well the toxicity of these other...

BACKGROUND: The acetaminophen risk analysis nomogram is used to predict hepatotoxicity risk in acute acetaminophen overdose based on a single plasma acetaminophen concentration (PAC) measured between 4 and 24 h after ingestion. There are case reports of patients with acute overdoses of acetaminophen combination ...

Acetaminophen has become a very popular over-the-counter analgesic in some countries and as a result it is used increasingly as an agent for self-poisoning. Without treatment only a minority of patients develop severe liver damage and 1 to 2% die in hepatic failure. Until Mitchell and his colleagues discovered the biochemical mechanisms of toxicity in 1973 ...

This study was conducted to examine the protective role of crude polysaccharide from brown seaweed Sargassum polycystum against acetaminophen-induced abnormality in blood glucose, serum albumin/globulin ratio, and liver glycogen, lactate, and pyruvate. Liver and renal tissue histology was performed to confirm the efficacy of Sargassum polysaccharide. A ...

The root of Arctium lappa Linne (A. lappa) (Compositae), a perennial herb, has been cultivated for a long time as a popular vegetable. In order to investigate the hepatoprotective effects of A. lappa, male ICR mice were injected with carbon tetrachloride (CCl4, 32 microl/kg, i.p.) or acetaminophen (600 mg/kg, i.p.). A. lappa suppressed the SGOT and SGPT elevations induced by ...

BackgroundThe development of effective therapies for acute liver failure (ALF) is limited by our knowledge of the pathophysiology of this condition, and the lack of suitable large animal models of acetaminophen toxicity. Our aim was to develop a reproducible invasively-monitored porcine model of acetaminophen-induced ALF.Method35kg ...

We encountered a decedent with an unexpected glioblastoma multiforme. A 61-year-old retired African-American woman was found dead in her home, fully clothed in her bathtub, with a pillow under her head. At autopsy, the brain showed a glioblastoma multiforme. Toxicology showed elevated hydrocodone, propoxyphene, acetaminophen, and positive paroxetine. The presence of a brain ...

Acetaminophen is an effective analgesic and antipyretic agent with few adverse effects when used in recommended dosages. The drug is metabolized mainly in the liver, and the several end products have no harmful effects. An intermediate compound in a minor metabolic pathway, however, is toxic; it is normally inactivated by glutathione. In the case of an ...

Caveolin-1 (Cav-1) is a membrane scaffolding protein, which functions to regulate intracellular compartmentalization of various signaling molecules. In the present studies, transgenic mice with a targeted disruption of the Cav-1 gene (Cav-1{sup -/-}) were used to assess the role of Cav-1 in acetaminophen-induced hepatotoxicity. Treatment of wild-type mice with ...

Caveolin-1 (Cav-1) is a membrane scaffolding protein which functions to regulate intracellular compartmentalization of various signaling molecules. In the present studies, transgenic mice with a targeted disruption of the Cav-1 gene (Cav-1^?/?) were used to assess the role of Cav-1 in acetaminophen-induced hepatotoxicity. Treatment of wild type mice with ...

N-Acetylcysteine is the drug of choice for the treatment of an acetaminophen overdose. It is thought to provide cysteine for glutathione synthesis and possibly to form an adduct directly with the toxic metabolite of acetaminophen, N-acetyl-p-benzoquinoneimine. However, these hypothese have not been tested in vivo, and other mechanisms ...

Despite extensive investigations, the cause of liver injury in 14% of patients with acute liver failure remains unknown (indeterminate). In a pilot study using a novel assay, highly specific acetaminophen-cysteine adducts were detected in 7 of 36 indeterminate patients (19%). To extend these observations, sera from 110 subjects enrolled in the Acute Liver Failure Study Group ...

While acetaminophen overdose has been recognized as a cause of alanine aminotransferase (ALT) elevations for over 40 years, recent studies have reported asymptomatic ALT elevations in research subjects who are administered with therapeutic doses (4 g/d or less) of acetaminophen for more than 4 days. While the clinical course of these elevations is not ...

Pre-clinical evidence demonstrates that neuropathic spinal cord injury (SCI) pain is maintained by a number of neurobiological mechanisms, suggesting that treatments directed at several pain-related targets may be more advantageous compared to a treatment focused on a single target. The current study evaluated the efficacy of the non-opiate analgesic ...

Pre-clinical evidence demonstrates that neuropathic spinal cord injury (SCI) pain is maintained by a number of neurobiological mechanisms, suggesting that treatments directed at several pain-related targets may be more advantageous compared to a treatment focused on a single target. The current study evaluated the efficacy of the non-opiate analgesic ...

The hepatotoxicant N-nitrosodimethylamine (NDMA) is presumed to exert toxicity through reactive metabolites. NDMA is similar in this respect to numerous other hepatotoxicants, for which hepatotoxicity is also associated with a rapid depletion of soluble and/or protein thiols, and an inhibition of calcium transport systems. The authors examined the hypothesis that ...

Paracetamol (acetaminophen, PCM) is widely used as an over-the-counter analgesic and antipyretic drug. Intake of a large dose of PCM may result in severe hepatic necrosis. Oxidative stress mediated by oxidative capacities of the PCM metabolite (N-acetyl-p-benzoquinoneimine (NAPQI), is considered as the main cause of hepatotoxicity of PCM. This work therefore seeks to induce ...

Febrile non-hemolytic and allergic reactions are the most common transfusion reactions, but usually do not cause significant morbidity. In an attempt to prevent these reactions, US physicians prescribe acetaminophen or diphenhydramine premedication before more than 50% of blood component transfusions. Acetaminophen and diphenhydramine are effective ...

We examined whether acetaminophen could alter renal oxidative stress induced by arsenic; also whether withdrawal of acetaminophen treatment can increase susceptibility of kidney to arsenic toxicity. Acetaminophen (400 and 1600 mg/kg) was co-administered orally to rats for 3 days after preexposure to arsenic (25 ...

A patient who allegedly consumed 100 tablets of an over-the-counter analgesic containing sodium acetylsalicylate, caffeine, and acetaminophen displayed no significant CNS stimulation despite the presence of 175 micrograms of caffeine per mL of serum. Because salicylates have been reported to augment the stimulatory effects of caffeine on the CNS, attention was focused on the ...

OBJECTIVE:: Hyperammonemia is a major contributing factor to the encephalopathy associated with liver disease. It is now generally accepted that hyperammonemia leads to toxic levels of glutamine in astrocytes. However, the mechanism by which excessive glutamine is toxic to astrocytes is controversial. Nevertheless, there is strong ...

Overdoses of acetaminophen cause hepato-renal oxidative stress. The present study was undertaken to investigate the protective effect of a 43 kDa protein isolated from the herb Cajanus indicus, against acetaminophen-induced hepatic and renal toxicity. Male albino mice were treated with the protein for 4 days (intraperitoneally, 2 mg/kg ...

Medicinal herbs have been used for centuries in an attempt to overcome hepatic dysfunctions emanating from ingestion of hepatotoxic substances. However, the vast majority of information concerning their use is anecdotal. Well-performed animal studies would lend credence to the concept that some medicinal herbs may prevent or, at least ameliorate, hepatic dysfunction arising from drug-induced ...

The present cell culture study investigated the effect of Ginkgo biloba extract pretreatment on acetaminophen toxicity and assessed the role of ginkgolide A and cytochrome P450 3A (CYP3A) in hepatocytes isolated from adult male Long-Evans rats provided ad libitum with a standard diet. Acetaminophen (7.5-25 mM for 24 h) conferred ...

Acetaminophen (Paracetamol), a most commonly used antipyretic/analgesic agent, is metabolized to AM404 (N-arachidonoylphenolamine) that inhibits uptake and degradation of anandamide which is reported to mediate the analgesic action of acetaminophen via CB1 receptor. AM404 and anandamide are also reported to produce anxiolytic-like behavior. In view of the ...

Page 1. Pediatric Focused Safety U d tpae: ... Alternative explanation lies in acetaminophen toxicity consistent with significant ALT and AST elevation (~ 6000 U/L) ...

This case recounts the story of a student who gave her cat half of a Tylenol tablet not knowing its potential harmful effects. The cat survives, but the incident motivates the student to learn more about the reaction mechanism underlying the liver toxicity of acetaminophen. The case outlines three possible reaction schemes that would explain the liver ...