Free Radical Damage and Lipid Peroxidation
Robert G. Meeks, Steadman D. Harrison, Richard J. Bull in Hepatotoxicology, 2020
The liver is subject to direct injurious attack by a wide variety of so-called primary hepatotoxins (Zimmerman, 1978) including alcohols; quinones; aliphatic and aromatic halogenated hydrocarbons; sulfur compounds; complex organic compounds of biological origin, e.g., phalloidin and aflatoxin; heavy metals; rare earths; elemental phosphorus; and many others. To our knowledge, in no case has a complete description been given for the biochemical and cell physiological mechanisms set into motion by the appearance of any primary hepatotoxin in the liver cell, nor for any case has a complete description been given for the full set of causes ultimately responsible for final cell death. To provide such a complete description turns out to be an exceedingly difficult and complex task. Within the context of the study of basic mechanisms, lipid peroxidation has attracted a great deal of attention. This is due in part to the wide range of xenobiotics known to cause peroxidative decomposition of liver lipids (Table 9-1, and see Kappus, 1987) and to the fact that lipid peroxidation is so destructive for biological membranes.
Use of Complementary and Alternative Therapies in Hepatic Disorders
Mary J. Marian, Gerard E. Mullin in Integrating Nutrition Into Practice, 2017
Notably, the consumption of red wine in patients with liver disease, however, is generally discouraged. According to the Dietary Guidelines for Americans,23 moderate alcohol consumption is defined as having up to one drink per day for women and up to two drinks per day for men. This definition is referring to the amount consumed on any single day and is not intended as an average over several days. Alcohol is a proven hepatotoxin as elucidated earlier. A standard drink is equal to 14.0 g (0.6 oz) of pure alcohol. Generally, this amount of pure alcohol is found in 5 oz of wine (12% alcohol content). Red wine contains on the order of 0.1–14.3 mg/L of resveratrol.24 Vitaglione et al. and Goldger et al. further studied the bioavailability of resveratrol and concluded the trace amounts of resveratrol reached in the blood are insufficient to explain its suspected ameliorating effects of alcohol. The metabolism and amount of resveratrol can be varying in wines and therefore, may benefit in healthy patients while patients with advanced liver disease may be harmed by red wine. Further studies are speculating that the cardiovascular benefits of wine appear to correlate with the content of procyanidins (flavanols).25
Diseases of the Hepatobiliary Tree and Pancreas Associated with Fever
Benedict Isaac, Serge Kernbaum, Michael Burke in Unexplained Fever, 2019
Malignant tumors — Hepatocellular carcinoma (HCC) is a common tumor in Africa, the Orient, and the South Pacific Islands, and not uncommon in Western countries. The most common manifestations of hepatocellular carcinoma are weight loss, malaise, anorexia, abdominal pain and fullness, and low-grade fever. A history of hepatitis B, aflatoxin, or other hepatotoxin ingestion may be contributory to the diagnosis. The presence of hepatomegaly with one or more nodular masses is suggestive. Some patients may complain of unexplained fever or FUO.172, 173 The fever has been attributed to central necrosis174 or bleeding within the tumor.175 A small percentage of patients have high fever and chills, which may simulate liver abscess.174 Rarely, there is intermittent jaundice, associated with colicky pain and fever, mimicking a common duct stone.175 Persistent HB antigenemia and a positive alpha-fetoprotein test are significant. Hepatic scanning may demonstrate one or more areas of decreased uptake when 99mTc-sulfur colloid is employed and increased activity when 67Ga citrate is administered.176 Ultrasonography may be useful in detecting echogenic masses. Computerized tomography alone is not usually diagnostic.177 Magnetic resonance imaging shows promise. However, the most definitive method of diagnosis is through needle biopsy of the liver, either blindly or under direct laparoscopic vision.
Combination of pomegranate extract and curcumin ameliorates thioacetamide-induced liver fibrosis in rats: impact on TGF-β/Smad3 and NF-κB signaling pathways
Published in Toxicology Mechanisms and Methods, 2020
Ayah M. H. Gowifel, Mona G. Khalil, Somaia A. Nada, Sanaa A. Kenawy, Kawkab A. Ahmed, Maha M. Salama, Marwa M. Safar
Thioacetamide (TAA) is a commonly used hepatotoxin in animal models, it has been used as a fungicide and organic solvent (Amin et al. 2012). Chronic administration of TAA can lead to liver fibrosis, liver cirrhosis, and HCC. The advantages of TAA as a model hepatotoxin include its high specificity for the liver, together with producing histological and biochemical alterations similar to those observed in human liver injury (Nada et al. 2015). The hepatotoxic effect of TAA is due to its metabolic activation by microsomal cytochrome P450 isozyme 2E1 (CYP2E1) to thioacetamide sulfoxide (TAASO), and further to a reactive metabolite, thioacetamide-S, S-dioxide (TAASO2), which binds covalently to liver macromolecules, leading to induction of oxidative stress, thus accelerating liver fibrosis (Li et al. 2012).
Using herbs medically without knowing their composition: are we playing Russian roulette?
Published in Current Medical Research and Opinion, 2022
Orly F. Kohn, Susie Q. Lew, Steve Siu-Man Wong, Ramin Sam, Hung-Chun Chen, Jochen G. Raimann, David J. Leehey, Antonios H. Tzamaloukas, Todd S. Ing
Many herbal medications have been identified to cause liver disorders such as hepatitis (acute, chronic and autoimmune), cholestasis, cirrhosis, vascular lesions and potentially even liver failure. Contaminations with microorganisms, pesticides, heavy metals, synthetic drugs and fungal toxins such as aflatoxin have been reported as the potential reasons20. Quan and co-authors identified two groups of hepatotoxins: the phyto-hepatotoxin group consists of phytochemicals and their metabolites produced naturally in plants, while the non-phyto-hepatotoxin group consists of contaminants or adulterants, e.g. pesticides21. Another contaminant, pyrrolizidine alkaloids (PA), has been found in over 6,000 plant species growing in countries all over the world. PAs with a double bond between C1 and C2 structure exhibit strong hepatotoxic, genotoxic, cytotoxic, neurotoxic and tumorigenic potentials. The consumption in error and in large amounts of plants with the 1,2 unsaturated PAs, can lead to severe liver injury by generation of radical metabolites via metabolism by the p450 (CYP) system22,23.
Acetaminophen is both bronchodilatory and bronchoprotective in human precision cut lung slice airways
Published in Xenobiotica, 2019
Joshua L. Kennedy, Richard C. Kurten, Sandra McCullough, Reynold A. Panettieri, Cynthia Koziol-White, Stacie M. Jones, Katherine Caid, Pritmohinder S. Gill, Dean Roberts, Hartmut Jaeschke, Mitchell R. McGill, Laura James
In addition to its beneficial effects, APAP is a dose-dependent hepatotoxin and is the leading cause of acute liver failure in the USA and Western Europe (Lee, 2008). Following high-dose exposure to APAP, depletion of hepatic glutathione and the formation of the reactive intermediate N-acetyl-p-benzoquinone imine (NAPQI) are recognized as the initiating events in the pathogenesis of liver injury (Hinson et al., 2010; McGill & Jaeschke, 2013). Other contributory mechanisms of liver injury include oxidative and nitrosative stress, mitochondrial injury, and inflammatory responses (Hinson et al., 2010; McGill & Jaeschke, 2013). The enzyme primarily responsible for the oxidative metabolism of APAP in the liver is CYP2E1. APAP is also metabolized in extra-hepatic tissues containing CYP2E1 such as the nasal epithelium, the pancreas, and the lung. In addition, CYP3A4 and CYP1A2 participate in the metabolism of APAP. The relationship of the extra hepatic metabolism of APAP in human disease or injury in other tissues is unknown.
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