Hexachlorobenzene (HCB) is a fungicide of well-known porphyrinogenic ability, which induces an experimental porphyria that resembles human porphyria cutanea tarda (PCT) in several animal species. It has been demonstrated that high glucose ingestion prevents porphyria development, and high-fat/high-protein diets enhance HCB porphyrinogenic ability. On the contrary, a diet rich in carbohydrates reduces HCB effects. The aim of this work was to study HCB effects on glycogen synthesis and degradation, as well as on glucose synthesis and transport, in order to elucidate whether would justify the beneficial use of carbohydrates in this porphyria. Rats were treated with HCB dissolved in corn oil (five daily doses 100mg/kg body weight). Results showed that: (1) HCB caused an increase in glycogen content; (2) glycogen synthase activity increased three times, and phosphorylase activity decreased about 40% due to fungicide intoxication. The effect of HCB on these two activities accounted for the higher glycogen content observed in treated animals; (3) three gluconeogenic enzymes were reduced 30-50%; (4) glucose uptake in the liver decreased in all weeks studied. The alterations found in glucose synthesis, its uptake in liver and other tissues, and its release from glycogen might contribute to the biochemical porphyria picture and would account for the effect of glucose above mentioned.
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http://dx.doi.org/10.1016/j.tox.2003.12.014 | DOI Listing |
JHEP Rep
July 2024
The Global NASH Council, Washington DC, USA.
Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL.
Methods: Members of the Global NASH Council created a survey about disease burden in NAFLD.
Clin Chem Lab Med
January 2025
Norwegian Porphyria Centre, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.
Objectives: An insulin resistant state is characteristic of patients with type 2 diabetes, polycystic ovary syndrome, and metabolic syndrome. Identification of insulin resistance (IR) is most readily achievable using formulae combining plasma insulin and glucose results. In this study, we have used data from the European Biological Variation Study (EuBIVAS) to examine the biological variability (BV) of IR using the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) and the Quantitative Insulin sensitivity Check Index (QUICKI).
View Article and Find Full Text PDFSemin Liver Dis
May 2024
Department of Experimental Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Front Genet
December 2023
Department of Endocrinology, Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan, Guangdong Province, China.
Acute intermittent porphyria (AIP) is a rare metabolic disorder that results from mutations in the gene encoding hydroxymethylbilane synthase (HMBS), an enzyme involved in heme biosynthesis. AIP follows an autosomal dominant inheritance pattern, but most carriers are asymptomatic. The clinical manifestations of AIP include acute attacks of abdominal pain and neuropsychiatric disturbances.
View Article and Find Full Text PDFSemin Liver Dis
November 2023
Department of Experimental Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
The porphyrias are a group of metabolic disorders that are caused by defects in heme biosynthesis pathway enzymes. The result is accumulation of heme precursors, which can cause neurovisceral and/or cutaneous photosensitivity. Liver is commonly either a source or target of excess porphyrins, and porphyria-associated hepatic dysfunction ranges from minor abnormalities to liver failure.
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