3,4-Methylenedioxyphenol (sesamol) is effective against acetaminophen-induced liver injury in rats. Whether sesamol's anti-hepatotoxic effect is comparable to that of N-acetylcysteine has never been studied. We investigated the anti-hepatotoxic effects of sesamol and N-acetylcysteine on acetaminophen-induced ...

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 ...

Urolithiasis, a condition in which stones are present in the urinary system, including the kidneys and bladder, is a poorly understood yet common disorder worldwide that leads to significant health care costs, morbidity, and work loss. Acetaminophen-induced liver damage is a major cause of death in patients with acute liver failure. Kidney and urinary ...

Urolithiasis, a condition in which stones are present in the urinary system, including the kidneys and bladder, is a poorly understood yet common disorder worldwide that leads to significant health care costs, morbidity, and work loss. Acetaminophen-induced liver damage is a major cause of death in patients with acute liver failure. Kidney and urinary ...

We have identified the xenobiotic receptor CAR (constitutive androstane receptor) as a key regulator of acetaminophen metabolism and hepatotoxicity. Known CAR activators as well as high doses of acetaminophen induced expression of three acetaminophen-metabolizing enzymes in wild-type but not in CAR-...

Acetaminophen (APAP) hepatotoxicity is the main cause of acute liver failure in humans. Although mitochondrial oxidant stress and induction of the mitochondrial permeability transition (MPT) have been implicated in APAP-induced hepatotoxicity, the link between these events is unclear. To investigate this, this study evaluated APAP ...

Acetaminophen (APAP) overdose is the most frequent cause of adult acute liver failure. Susceptibility or resistance to APAP toxicity is most likely accounted for by the interplay of several factors. One factor important in multiple different chronic liver diseases that may play a role in APAP toxicity is elevated hepatic iron. Hereditary hemochromatosis is traditionally ...

It has been reported that dietary polyunsaturated fats (PUFA) increase liver injury in response to ethanol feeding. We tested the hypothesis that diets rich in linoleic acid (18:2n-6) would affect acute liver injury after acetaminophen injection and that protein restriction might exacerbate the liver injury. We examined effects of feeding diets with either 15% (wt/wt) corn oil ...

Severe acute liver injury due to accidental or intentional acetaminophen overdose presents a major clinical dilemma often requiring liver transplantation. In the present study, liver regeneration after profound liver injury in mice challenged with acetaminophen was facilitated by the exogenous addition of ELR-containing CXC chemokines such as macrophage inflammatory protein-2 ...

Acetaminophen overdose causes acute liver injury or even death in both humans and experimental animals. We investigated the effect of 17?-estradiol against acetaminophen-induced acute liver injury and mortality in mice. Male mice were given acetaminophen (p-acetamidophenol; 300 mg/kg; orally) to induce acute liver ...

BackgroundAcetaminophen (AAP) is widely prescribed for treatment of mild pain and fever in western countries. It is generally considered a safe drug and the most frequently reported adverse effect associated with acetaminophen is hepatotoxicity, which generally occurs after acute overdose. During AAP overdose, encephalopathy might develop and contribute to ...

The cell death receptor Fas plays a role in the establishment of fulminant hepatitis, a major cause of drug-induced liver failure. Fas activation elicits extrinsic apoptotic and hepatoprotective signals; however, the mechanisms by which these signals are integrated during disease are unknown. Tissue inhibitor of metalloproteinases 3 (TIMP3) controls the critical sheddase a disintegrin and ...

The methanol extract of the leaves of Centaurium erythraea L. (Gentianaceae) was evaluated for hepatoprotective activity against acetaminophen-induced liver toxicity in rats. An oral dose of 300 mg/kg/day for 6 days or a single dose of 900 mg/kg for 1 day exhibited a significant protective effect by lowering serum glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate ...

Acetaminophen-induced liver toxicity is the most frequent precipitating cause of acute liver failure and liver transplant, but contemporary medical practice has mainly focused on patient management after a liver injury has been induced. An integrative genetic, transcriptional, and two-dimensional NMR-based metabolomic analysis performed using multiple ...

Acetaminophen-induced liver toxicity is the most frequent precipitating cause of acute liver failure and liver transplant, but contemporary medical practice has mainly focused on patient management after a liver injury has been induced. An integrative genetic, transcriptional, and two-dimensional NMR-based metabolomic analysis performed using multiple ...

Ozone (O(3)), an oxidant air pollutant in photochemical smog, principally targets epithelial cells lining the respiratory tract. However, changes in gene expression have also been reported in livers of O(3)-exposed mice. The principal aim of the present study was to determine if acute exposure to environmentally relevant concentrations of O(3) could cause exacerbation of ...

Ozone (O₃), an oxidant air pollutant in photochemical smog, principally targets epithelial cells lining the respiratory tract. However, changes in gene expression have also been reported in livers of O₃-exposed mice. The principal aim of the present study was to determine if acute exposure to environmentally relevant concentrations ...

The immune system is alerted to cell death by molecules known as damage-associated molecular patterns (DAMPs). These molecules partly mediate acetaminophen-induced liver injury, an archetypal experimental model of sterile cell death and the commonest cause of acute liver failure in the western world. Cyclophilin A (CypA) is an intracellular protein that is ...

Although it is a commonly used analgesic, acetaminophen can be highly hepatotoxic. This study seeks to further investigate the mechanisms involved in acetaminophen-induced hepatotoxicity, as well as the role of CXCR2 receptor/ligand interactions in the liver�s response to and recovery from acetaminophen toxicity. The CXC chemokines and their receptor, ...

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 acetaminophen ...

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 ...

... Activity levels were determined at 16, 24, 48 and 72 hours after intraperitoneal administra- tion of the toxic agents to rats. ...

... Activity levels were determined at 16, 24, 48, and 72 hours after intraperitoneal administration of the toxic agents to rats. ...

We present a case of a 14-year-old previously healthy boy with acute hepatotoxicity after noni berry juice consumption. As the popularity of noni berry consumption continues to increase, heightened awareness of the relation between noni berry consumption and acute hepatotoxicity is important. PMID:21119544

The fruit of Cornus officinalis Sieb. et Zucc. is commonly prescribed in Asian countries as a tonic formula. In this study, the hepatoprotective effect of ethanolic extracts of the fruit of C. officinalis (ECO) was investigated in a mouse model of acetaminophen- (APAP-) induced liver injury. Pretreatment of mice with ECO (100, 250, and 500?mg/kg for 7 days) significantly prevented the APAP ...

The fruit of Cornus officinalis Sieb. et Zucc. is commonly prescribed in Asian countries as a tonic formula. In this study, the hepatoprotective effect of ethanolic extracts of the fruit of C. officinalis (ECO) was investigated in a mouse model of acetaminophen- (APAP-) induced liver injury. Pretreatment of mice with ECO (100, 250, and 500?mg/kg for 7 days) significantly prevented the APAP ...

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 several genes involved in phase II and phase III xenobiotic ...

The acute hepatotoxicity and response of hepatic cytochrome P450 to treatment with the three isomers of dichlorobenzene (DCB) have been investigated. The objectives were to estimate the onset of toxicity and to further elucidate the role of cytochrome P45...

Precision-cut liver slices (PCLS) preserve the tissular organization of the organ and represent an in vitro model closer to in vivo conditions than hepatocytes cultures. As this may be an interesting tool not only for the investigation of hepatotoxic and protective effects but also for bioguided fractionations schemes, the usefulness of PCLS was compared with an in vivo test ...

Nuclear transcription factors, such as NF-kB and NF-IL6, are believed to play an important role in regulating the expression of genes that encode for products involved in tissue damage and inflammation and, thus, may represent early biomarkers for chemical toxicities. In the present study changes in DNA binding activity of these factors were examined in livers of mice administered ...

The toxicity of monochlorobenzene (CB) was investigated in rainbow trout following acute intraperitoneal (i.p.) administration and chronic exposure via the water in a continuously flowing system for 15 or 30 days. In the acute study overt toxicity and hepatotoxicity was monitored...

AIM: To examine the effects of 2,4-dihydroxybenzophenone (BP-1), a benzophenone derivative used as an ultraviolet light absorbent, on acetaminophen (APAP)-induced hepatotoxicity in C57BL/6J mice.METHODS: Mice were administered orally with BP-1 at doses of 200, 400 and 800 mg/kg body weight respectively every morning for 4 d before a hepatotoxic dose of ...

OBJECTIVE: Acetaminophen (APAP), an antipyretic/analgesic drug, is reported to cause toxicity on overdose. Dietary supplements are currently being explored to decrease toxicity. In the present study, the protective effect of probiotic Enterococcus lactis IITRHR1 was evaluated at different doses (10(7), 10(8), and 10(9) colony-forming units) against APAP-induced liver damage. METHODS: Male Wistar ...

The circadian clock gene Period2 (Per2) plays important roles in many physiologic and pathologic processes in mammals. In the previous study, we have reported the protective role of mPer2 against carbon tetrachloride induced hepatotoxicity. Here, we further explore the contribution of this gene to acetaminophen (APAP) induced liver injury in mice. It is reported that the ...

The frequent use of rodent hepatic in vitro systems in pharmacological and toxicological investigations challenges extrapolation of in vitro results to the situation in vivo and interspecies extrapolation from rodents to humans. The toxicogenomics approach may aid in evaluating relevance of these model systems for human risk assessment by direct comparison of toxicant-induced gene expression ...

Acetaminophen (APAP) is safe at therapeutic levels but causes hepatotoxicity via N-acetyl-p-benzoquinone imine-induced oxidative stress upon overdose. To determine the effect of human (h) pregnane X receptor (PXR) activation and CYP3A4 induction on APAP-induced hepatotoxicity, mice humanized for PXR and CYP3A4 (TgCYP3A4/hPXR) were treated with APAP ...

The present study was undertaken to examine the protective effects of an anthocyanin fraction (AF) obtained from purple-fleshed sweet potato on acetaminophen (paraceptamol [APAP])-induced hepatotoxicity in mice and to determine the mechanism involved. Mice pretreated with AF prior to APAP administration showed significantly lower increases in serum alanine aminotransferase and ...

In overdose the analgesic/antipyretic acetaminophen (APAP) is hepatotoxic. Toxicity is mediated by initial hepatic metabolism to N-acetyl-p-benzoquinone imine (NAPQI). After low doses NAPQI is efficiently detoxified by GSH. However, in overdose GSH is depleted, NAPQI covalently binds to proteins as APAP adducts, and oxygen/nitrogen stress occurs. Toxicity is believed to occur ...

In rats pretreated with either phenobarbital (PB) or with polychlorinated biphenyl (PCB), an acute hepatotoxic reaction developed within 24 hr of inhalation exposure to vinylidene fluoride (VDF:1,1-difluoroethylene). PCB is much more effective than PB in this sensitizaion, which was evaluated by measurement of liver weight, serum sorbitol dehydrogenase ...

Because of the ubiquitous presence of p-xylene in air and the existing uncertainty regarding its hepatotoxic potential, we examined the effect of acute and short-term exposure to Inhaled p-xylene on the liver. ale F344 rats were exposed to 0 or to 1600 ppm p-xylene, 6 hr/day, for...

Context. The risk of hepatotoxicity secondary to acute acetaminophen overdose is related to serum acetaminophen concentration and lag time from ingestion to N-acetylcysteine (NAC) therapy. Psi (Greek letter ?) is a toxicokinetic parameter that takes the acetaminophen level at 4 h post-ingestion ([APAP](4 h)) and the time-to-initiation of NAC (tNAC) into ...

Aldo-keto reductase-7A (AKR7A) is an enzyme important for bioactivation and biodetoxification. Previous studies suggested that Akr7a might be transcriptionally regulated by oxidative stress-responsive transcription factor nuclear factor erythroid 2 p45-related factor 2 (Nrf2), a protein highly responsive to acetaminophen (APAP) or its intermediate metabolite, N-acetyl-p-benzoquinoneimine (NAPQI). ...

The toxicity of vinylidene chloride (VDC) was studied in mice and rats exposed to various concentrations of the vapors for 23 hr/day. In addition, the ability of various treatments to alter parameters of toxicity was evaluated. Mice were more sensitive than rats both to the acute lethal and hepatotoxic effects of VDC. Disulfiram treatment reduced the ...

This study investigated the possible protective effects and mechanism of rhein on Acetaminophen (APAP)-induced hepatotoxicity and nephrotoxicity in rats. Treatment of rats with APAP resulted in severe liver and kidney injuries, as demonstrated by drastic elevation of serum glutamate-pyruvate transaminase (GPT), glutamate-oxaloacetic transaminase (GOT), total bilirubin (TBIL), ...

Oxidative stress is an important factor in drug induced hepatotoxicity and antioxidants from natural sources have potential to ameliorate it. The present study was aimed to investigate cyto-protective potential of probiotic Enterococcus lactis IITRHR1 (El(SN)) and Lactobacillus acidophilus MTCC447 (La(SN)) lysate against acetaminophen (APAP) induced ...

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 ...

Kava is traditionally consumed by South Pacific islanders as a drink and became popular in Western society as a supplement for anxiety and insomnia. Kava extracts are generally well tolerated, but reports of hepatotoxicity necessitated an international reappraisal of its safety. Hepatotoxicity can occur as an acute, severe form or a ...

Kava is traditionally consumed by South Pacific islanders as a drink and became popular in Western society as a supplement for anxiety and insomnia. Kava extracts are generally well tolerated, but reports of hepatotoxicity necessitated an international reappraisal of its safety. Hepatotoxicity can occur as an acute, severe form or a ...

The acute hepatotoxicity and response of hepatic cytochrome P450 to treatment with the three isomers of dichlorobenzene (DCB) have been investigated. The objectives were to estimate toxic thresholds and to further e1ucidate the role of cytochrome P450 in the metabolism and toxici...

Drug hepatotoxicity is the most common cause of fulminant hepatic failure in the USA. We describe a rare case of a patient who developed an acute liver injury after initiation of therapy with quetiapine, but after conservative management and a trial of steroids, has fully recovered. This is the second reported case of quetiapine-induced liver injury in the ...

Procedures were developed to clinically evaluate liver damage and liver function in rainbow trout following either acute intraperitoneal (i.p.) treatment or subacute bath exposure to selected mammalian hepatotoxic agents. Elevations in serum of liver spec...

Procedures were developed to clinically evaluate liver damage and liver function in rainbow trout following either acute intraperitoneal (i.p.) treatment or subacute bath exposure to selected mammalian hepatotoxic agents. Elevations in serum of liver specific enzymes such as aspa...

A 42-year-old woman developed jaundice due to acute hepatitis several weeks after ingestion of a herbal preparation containing greater celandine (Chelidonium majus) and curcuma root, which had been prescribed by an alternative therapist due to a skin complaint. After the medication had been withdrawn, clinical recovery was rapid and the hepatic functions returned to normal ...

The impact of liver transplantation on the survival in fulminant hepatic failure was evaluated in a retrospective study including 87 patients admitted to Rigshospitalet over a three and a half year period before and a three and a half year period after the Danish liver transplantation programme was started. The number of admissions increased by 178% in the second period. Fifty-two percent of the ...

The protective effect of the phenolic compound syringic acid, one of the major benzoic acid derivatives from edible plants and fruits, was evaluated against acetaminophen (APAP)-induced hepatotoxicity in rats. Toxicity was induced in adult male albino Wistar rats by the administration of APAP (750 mg/kg body weight) intraperitoneally. Rats were treated with syringic acid (25, ...

The constitutive androstane receptor (CAR) regulates transcription of phenobarbital-inducible genes that encode xenobiotic-metabolizing enzymes in liver. CAR is localized to the hepatocyte cytoplasm but to be functional, it translocates into the nucleus in the presence of phenobarbital-like CAR ligands. We now demonstrate that adenovirally driven EGFP-CAR, as expected, translocates into the ...

CDDO-Im is a synthetic triterpenoid recently shown to induce cytoprotective genes through the Nrf2-Keap1 pathway, an important mechanism for the induction of cytoprotective genes in response to oxidative stress. Upon oxidative or electrophilic insult, the transcription factor Nrf2 translocates to the nucleus, heterodimerizes with small Maf proteins, and binds to antioxidant response elements ...

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 ...

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 ...

Increase dincidences of hepatotoxicity have been observed in diabetic patients receiving drug therapies. Neither the mechanisms nor the predisposing factors underlying hepatotoxicity in diabetics are clearly understood. Animal studies designed to examine the mechanisms of diabetes-modulated hepatotoxicity have traditionally focused ...

Dietary supplements represent an increasingly common source of drug-induced liver injury. Hydroxycut is a popular weight loss supplement which has previously been linked to hepatotoxicity, although the individual chemical components underlying liver injury remain poorly understood. We report two cases of acute hepatitis in the setting of Hydroxycut ...

Hepatotoxicity is regarded as a rare side effect of amphotericin B therapy. A patient with acute myelogenous leukemia who had normal liver function was treated with amphotericin B for fungal pneumonia. While he was receiving the drug at high dosages asymptomatic elevation of the levels of alkaline phosphatase, serum glutamic oxaloacetic transaminase, serum ...

We describe the first reported case of biopsy proven hepatotoxicity associated with the natural male enhancement supplement, Enzyte. The patient's symptoms and liver function tests resolved with cessation of the popular "mail order" drug that contains many herbal ingredients. The case highlights the need to be alert to the possibility of herbal supplements and Enzyte ...

Acetaminophen (AP) is a widely used, cheap, and over-the-counter nonsteroidal anti-inflammatory drug. Its toxicity depends on the cytochrome P-450 (CYP)-mediated oxidation to the toxic metabolite N-acetyl-p-benzoquinoneimine. On the other hand, arsenic, a global groundwater and environmental contaminant of major public health concern, decreases hepatic CYP content and its dependent monoxygenase ...

Older age is considered a poor prognostic factor in acute liver failure (ALF) and may still be considered a relative contraindication for liver transplantation for ALF. We aimed to evaluate the impact of older age, defined as age ? 60 years, on outcomes in patients with ALF. One thousand one hundred twenty-six consecutive prospective patients from the US ...

Antibiotics used by general practitioners frequently appear in adverse-event reports of drug-induced hepatotoxicity. Most cases are idiosyncratic (the adverse reaction cannot be predicted from the drug's pharmacological profile or from pre-clinical toxicology tests) and occur via an immunological reaction or in response to the presence of hepatotoxic ...

Antibiotics used by general practitioners frequently appear in adverse-event reports of drug-induced hepatotoxicity. Most cases are idiosyncratic (the adverse reaction cannot be predicted from the drug's pharmacological profile or from pre-clinical toxicology tests) and occur via an immunological reaction or in response to the presence of hepatotoxic ...

The use of complementary and alternative medicines is becoming increasingly popular in Western society. As a result the number of reported adverse reactions is increasing. Glucosamine is a herbal remedy commonly used to ease joint pain in osteoarthritis, and only two previous reports of hepatotoxicity have been published in the scientific literature. The present report ...