283 results match your criteria: "Halothane Hepatotoxicity"

Article Synopsis
  • Prolonged use of Highly Active Antiretroviral Therapy (HAART) can cause liver toxicity, with limited treatment options for hepatic cell regeneration.
  • A study assessed the protective effects of Methanol fruit extract (MFEPG) on rats undergoing HAART, revealing that MFEPG helped restore normal liver function and reduced oxidative damage indicators.
  • The findings suggest that MFEPG has antioxidant properties capable of mitigating HAART-induced liver injury, but further research is necessary to confirm its safety and efficacy.
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Article Synopsis
  • Drug-induced liver injury, often caused by drugs like acetaminophen, can be severe, and the study examines how the pattern recognition receptor A (SRA) influences this process through immune interactions.
  • Mice lacking SRA show increased sensitivity to liver damage, which is linked to reduced levels of the protective cytokine IL-10 and heightened liver inflammation.
  • The research suggests that SRA plays a critical role in protecting the liver by promoting IL-10 production in immune cells, pointing to potential new approaches for treating drug-induced liver injuries.
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Article Synopsis
  • Patients with malignant hyperthermia (MH) can experience myopathy symptoms like muscle pain and fatigue outside of anesthesia, and oral dantrolene might help alleviate these symptoms, but high doses can cause liver damage.
  • A study of 476 MH-susceptible patients showed that 164 received dantrolene, with mild to moderate side effects reported in 28% and 13% discontinuing treatment due to these effects or lack of improvement.
  • Most patients (87%) adhered to the therapy and reported improvements, especially those with a history of MH, highlighting the effectiveness of dantrolene for certain patients despite some adverse effects.*
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Article Synopsis
  • Hepatotoxicity from volatile anesthetics is rare but clinically important due to their common use, unpredictable onset, and potential severity.
  • Halothane is the anesthetic most associated with liver dysfunction, particularly upon re-exposure, while cases involving sevoflurane are very uncommon.
  • A 1-year-old girl developed severe acute hepatitis and died after surgery with sevoflurane, leading to the case's serious classification in national and European pharmacovigilance systems to enhance patient safety and inform medical literature.
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Fluorine-Containing Inhalation Anesthetics: Chemistry, Properties and Pharmacology.

Curr Med Chem

December 2020

School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 205 Luoshi Road, Wuhan 430070, China.

Article Synopsis
  • This review summarizes research on the synthesis, chemistry, and pharmacology of fluorinated inhalation anesthetics, highlighting their historical development and increasing use of fluorine and ether structures.
  • Halothane, an older anesthetic, caused severe liver toxicity, leading to enflurane's introduction in the 1970s, followed by isoflurane in the 1980s, which offered some improvements.
  • Despite advancements with desflurane and sevoflurane in the 1990s providing lower toxicity and better anesthetic properties, developing even better options remains difficult due to challenges in predicting anesthetic activity from molecular structures and various synthetic hurdles.
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Drug-induced liver injury in obesity and nonalcoholic fatty liver disease.

Adv Pharmacol

February 2020

INSERM, Univ. Rennes, INRA, Institut NUMECAN (Nutrition Metabolisms and Cancer) UMR_A 1341, UMR_S 1241, Rennes, France. Electronic address:

Article Synopsis
  • Obesity is linked to nonalcoholic fatty liver disease (NAFLD), which can progress from a benign condition (NAFL) to more severe forms like nonalcoholic steatohepatitis (NASH) and even liver cancer.
  • *Certain genetic and environmental factors can accelerate the transition from simple fatty liver to NASH, increasing the risk of drug-induced liver injury in obese patients.
  • *The review discusses specific drugs, including acetaminophen and methotrexate, that pose heightened risks for liver damage in individuals with obesity and NAFLD, highlighting the need to identify these pharmaceuticals to prevent acute or chronic liver complications.
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Article Synopsis
  • - The rise of electric equipment in operating rooms increased fire risks with flammable agents like ether and cyclopropane, leading to concerns about cardiac issues and liver damage associated with chloroform.
  • - Halothane was introduced in the late 1950s as a safer alternative, and the manufacturer Ayerst Laboratories disclosed its major risks, specifically cardiac arrhythmias and hepatotoxicity, to regulatory bodies and practitioners in a timely manner.
  • - Despite the lengthy and costly drug approval process, the manufacturer’s transparency about halothane's risks allowed it to be widely used for decades until newer options with improved safety profiles emerged.
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Article Synopsis
  • Drug-induced liver injury in children (cDILI) is rare, making up about 1% of all adverse drug reactions and a significant portion of acute liver failure cases in kids, but studies show that their susceptibility might be more drug-specific than previously assumed.
  • Certain drugs, such as valproic acid and dactinomycin, are more likely to cause cDILI, while others, like deferasirox and isoniazid, are associated with liver injury in adults (aDILI) instead.
  • There is a critical knowledge gap in understanding the differences in how children and adults react to liver injuries caused by medication, as current animal models and diagnostic tools are lacking.
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Article Synopsis
  • Obesity is linked to nonalcoholic fatty liver disease (NAFLD), which can lead to different liver issues and affects how drugs can harm the liver, increasing the risk of drug-induced liver injury (DILI).
  • The review aims to compile information on how NAFLD may heighten the risk of drug-induced hepatotoxicity by analyzing various studies and their findings.
  • Certain drugs, like acetaminophen and methotrexate, are particularly risky for obese patients, and there’s a need for more research to identify additional pharmaceuticals that could worsen liver health in those with obesity and NAFLD.
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Article Synopsis
  • This study investigates the roles of caspase-8 and -9 in drug-induced liver injury (DILI) caused by CYP2E1 metabolites using rat models and human liver cell cultures exposed to carbon tetrachloride, halothane, and sevoflurane.
  • In vivo results showed no liver dysfunction after sevoflurane exposure, but carbon tetrachloride and halothane led to increased liver damage indicators and caspase activities, indicating hepatotoxicity in both studies.
  • CYP2E1-related compounds significantly contribute to the toxicity of halogenated hydrocarbons, suggesting that monitoring caspase-8 and -9 activities could serve as new
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Article Synopsis
  • The study aimed to replace halothane with sevoflurane in a rat model of asphyxia cardiac arrest (ACA) to reduce health risks and align with clinical practices, given halothane's toxicity.
  • Adult rats underwent ACA followed by resuscitation, with observations on vital signs and blood parameters during recovery, and brain tissue evaluated after 7 days.
  • Results showed that sevoflurane anesthetized rats had better heart rate and blood pressure, along with reduced neurological damage in the hippocampus compared to those treated with halothane, validating the model's effectiveness despite necessary adjustments.
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Drug-induced allergic hepatitis develops in mice when myeloid-derived suppressor cells are depleted prior to halothane treatment.

Hepatology

August 2015

Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.

Article Synopsis
  • Clinical evidence suggests that serious drug-induced liver injuries may be caused by the adaptive immune system reacting to drug-protein complexes, a condition known as drug-induced allergic hepatitis, though specific animal models have been lacking.
  • In a study with female Balb/cJ mice, researchers observed liver damage and immune cell infiltration after exposure to halothane, indicating that immune tolerance in the liver can be disrupted.
  • The findings point to potential mechanisms for drug-induced allergic hepatitis that could help develop animal models for further research and suggest that a breakdown in liver tolerance might make individuals more susceptible to this condition.
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Hepatotoxicity of halogenated inhalational anesthetics.

Iran Red Crescent Med J

September 2014

Department of Molecular Hepatology, Middle East Liver Disease Center, Tehran, IR Iran ; Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, IR Iran.

Article Synopsis
  • * A review of 52 studies from 1966 to 2013 confirmed that all halogenated anesthetics, like halothane and enflurane, can cause liver damage, particularly through a metabolic pathway involving cytochrome P-450 2E1, while sevoflurane appears to have a lower risk.
  • * Although liver toxicity from these anesthetics is not common, it is essential to acknowledge the potential link, especially with older agents like halothane compared to newer ones with lower hepatotoxicity.
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Involvement of miRNAs in the early phase of halothane-induced liver injury.

Toxicology

May 2014

Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan; Department of Drug Safety Sciences, Nagoya University School of Medicine, Nagoya 466-8550, Japan. Electronic address:

Article Synopsis
  • * This study investigates the effects of the hepatotoxic drug halothane (HAL) on miRNA expression in mice, finding significant changes in miRNA levels related to inflammation and liver injury within 24 hours after dosing.
  • * The researchers identified miR-106b as a crucial miRNA whose down-regulation leads to the up-regulation of STAT3, contributing to the development of HAL-induced liver injury.
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Formation/fate of reactive metabolites from general anesthetics and a comparison of toxic and non-toxic analogues: a DFT study.

Drug Metab Lett

October 2013

Department of Medicinal Chemistry, Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, (NIPER), Sector-67, S. A. S. Nagar - 160 062, Punjab, India.

Article Synopsis
  • Chloroform and Halothane are anesthetics known to cause liver damage due to their reactive metabolites, although the specific molecular reactions leading to these metabolites haven't been thoroughly studied yet.
  • Quantum chemical methods revealed that the reaction of chloroform with HOOH to form phosgene is highly exothermic and has a low activation barrier, suggesting the reaction is likely to occur easily.
  • Comparison of bond dissociation and radical stabilization energies between chloroform, halothane, and safer anesthetics indicates that these energy metrics can help identify toxic versus non-toxic anesthetics.
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Mechanism of exacerbative effect of progesterone on drug-induced liver injury.

Toxicol Sci

March 2012

Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.

Article Synopsis
  • Drug-induced liver injury (DILI) is a significant issue in drug development, with female mice showing worse outcomes, particularly influenced by hormones like progesterone.
  • Research indicates that progesterone worsens liver injury in female mice by increasing immune cell infiltration and inflammatory mediator levels through the activation of the ERK pathway and Kupffer cells.
  • Targeting progesterone receptors and reducing immune responses may offer new therapeutic strategies to manage DILI in females.
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Article Synopsis
  • - Halothane, introduced in the 1950s as an anesthetic, led to concerns about liver damage (hepatitis), prompting the search for safer alternatives with fewer side effects.
  • - Two types of halothane-related liver damage were identified: mild hepatitis (type 1) with self-limiting symptoms, and severe hepatotoxicity (type 2), often resulting in acute liver failure.
  • - Newer anesthetics like enflurane, sevoflurane, and desflurane, which aren't metabolized by the liver and cause fewer adverse reactions, are more expensive, raising challenges for their adoption in lower-budget healthcare systems.
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Article Synopsis
  • Severe liver damage from halothane (HAL) occurs in a small percentage of patients, with female sex identified as a risk factor; the mechanism behind this is unclear.
  • In a study with female BALB/cJ mice, HAL treatment led to significant liver injury that varied with the estrous cycle, while ovariectomized (OVX) mice experienced only mild injury.
  • Elevated levels of interferon-gamma (IFN-γ) and activated natural killer (NK) cells were linked to severe liver injury, indicating that these immune responses are critical factors in the heightened sensitivity of females to HAL-induced hepatotoxicity.
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A mouse model of severe halothane hepatitis based on human risk factors.

J Pharmacol Exp Ther

May 2010

Cellular and Molecular Biology Program, Michigan State University, East Lansing, Michigan 48824, USA.

Article Synopsis
  • Halothane is an inhaled anesthetic that can cause severe liver injury, known as "halothane hepatitis," affecting about 1 in 20,000 patients, with specific risk factors identified such as female sex and genetics.
  • Researchers developed a mouse model to mimic human halothane hepatitis, finding that female mice were more prone to serious liver damage compared to males, especially under fasting conditions.
  • The study revealed that the severity of liver injury in female mice was linked to a stronger immune response, highlighting the importance of neutrophils in the liver damage caused by halothane exposure.
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Article Synopsis
  • * Sevoflurane is generally thought to have low potential for causing liver problems due to its metabolism process.
  • * However, a case is reported where a 67-year-old woman experienced acute liver dysfunction following anesthesia with sevoflurane, indicating that it may still pose risks in certain circumstances.
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Article Synopsis
  • Drug-induced liver injury poses significant challenges in both drug development and clinical therapy, often with unknown mechanisms making prediction difficult.
  • Using a mouse model, researchers compared immune responses in two mouse strains (BALB/c and C57BL/6) to study how halothane, an anesthetic, affects liver health.
  • The study found that interleukin-17 (IL-17) is involved in liver injury caused by halothane, with increased IL-17 levels leading to heightened liver damage, indicating its potential role in this type of injury.
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