Patients with Wilson's disease (WD), Indian childhood cirrhosis (ICC), and idiopathic copper toxicosis (ICT) develop severe liver disease morphologically characterized by ballooning of hepatocytes, inflammation, cytoskeletal alterations, and Mallory body (MB) formation, finally leading to mostly micronodular cirrhosis. The pathogenesis of MBs in copper toxicosis is still unresolved. Immunohistochemical analysis of MBs in different types of copper intoxication revealed that keratin, p62, and ubiquitin are integral components. Thus MBs associated with copper intoxication resemble those present in alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH). p62 is a multifunctional immediate early gene product that, on the one hand, is involved in stress-induced cell signaling (particularly that of oxidative stress) by acting as an adapter protein linking receptor-interacting protein (RIP) with the atypical protein kinase C. On the other hand, p62 binds with high affinity to polyubiquitin and ubiquitinated proteins. In conclusion, p62 accumulation in WD, ICC, and ICT and deposition in MBs indicates a central role of protein misfolding induced by oxidative stress in copper-induced liver toxicity. By sequestering potentially harmful misfolded ubiquitinated proteins as inert cytoplasmic inclusion bodies (e.g., as MBs), p62 may be a major player in an important cellular rescue mechanism in oxidative hepatocyte injury.
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http://dx.doi.org/10.1002/hep.20108 | DOI Listing |
Open Vet J
April 2024
Department of Pathology and Laboratory Diagnosis, College of Veterinary Medicine, Qassim University, Buraidah, Saudi Arabia.
Background: Bloody urine is classified in farm animals as hematuria, hemoglobinuria, and myoglobinuria. In small ruminants, discolored urine is reported due to several etiologies which is sometimes fatal. Of these causes are babesiosis, bacillary hemoglobinuria, copper toxicity, and hypophosphatemia.
View Article and Find Full Text PDFJ S Afr Vet Assoc
March 2024
Department of Production Animal Studies, Faculty of Veterinary Science, University of Pretoria, South Africa.
In southern Africa game farming has become an effective way of using underutilised resources and a valuable method of preserving and increasing wildlife numbers. However, little is known about the mineral requirements of wild animal species or the assessment of the mineral nutritional status of these species. To establish criteria for estimating the copper (Cu) nutritional status of wildlife, current knowledge about Cu metabolism and criteria for domestic animals has been used.
View Article and Find Full Text PDFVirchows Arch
April 2024
Diagnostic and Research Institute of Pathology, Diagnostic & Research Center of Molecular Biomedicine, Medical University of Graz, Neue Stiftingtalstrasse 6, A-8010, Graz, Austria.
Mallory-Denk bodies (MDBs) are hepatocellular cytoplasmic inclusions, which occur in certain chronic liver diseases, such as alcohol-related (ASH) and metabolic dysfunction-associated (MASH) steatohepatitis, copper toxicosis, some drug-induced liver disorders, chronic cholangiopathies, and liver tumors. Our study focused on the expression of the senescence markers p21 and p16 in hepatocytes containing MDBs in steatohepatitis, chronic cholangiopathies with fibrosis or cirrhosis, Wilson's disease, and hepatocellular carcinomas. Cytoplasm and nuclei of MDB-containing hepatocytes as well as MDB inclusions, except those associated with carcinoma cells, were strongly p16-positive, p21-positive, as well as p21-negative nuclei in MDB-containing hepatocytes which were observed whereas MDBs were p21-negative.
View Article and Find Full Text PDFFoods
November 2023
Institute of Plant Protection, Hungarian University of Agriculture and Life Sciences, Georgikon Campus, Deák F. u. 16, 8360 Keszthely, Hungary.
The popularity of seafoods is high due to their superb dietary properties and healthy composition. However, it is crucial to understand whether they adequately contribute to our essential nutritional needs. Small amounts of essential metals are indispensable in the human body to proper physiological functioning; their deficiency can manifest in various sets of symptoms that can only be eliminated with their intake during treatment or nutrition.
View Article and Find Full Text PDFVet Rec
February 2024
Department of Veterinary Medicine, Queen's Veterinary School Hospital, University of Cambridge, Cambridge, UK.
Background: Copper-associated chronic hepatitis (CuCH) is poorly characterised in Cavalier King Charles spaniels (CKCS).
Methods: Hepatic copper accumulation was qualitatively and quantitatively assessed, and blood samples were used for genetic testing to screen for known CuCH-associated genetic variants.
Results: The study included 13 CKCS with CuCH and eight unaffected controls.
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