Vitamin D 3 supplementation alleviates chemically-induced cirrhosis-associated hepatocarcinogenesis.

Autor: Goto RL; São Paulo State University (UNESP), Biosciences Institute, Department of Structural and Functional Biology, Botucatu, SP, Brazil., Tablas MB; São Paulo State University (UNESP), Biosciences Institute, Department of Structural and Functional Biology, Botucatu, SP, Brazil., Prata GB; São Paulo State University (UNESP), Medical School, Department of Pathology, Botucatu, SP, Brazil., Espírito Santo SG; São Paulo State University (UNESP), Medical School, Department of Pathology, Botucatu, SP, Brazil., Fernandes AAH; São Paulo State University (UNESP), Biosciences Institute, Department of Chemical and Biological Sciences, Botucatu, SP, Brazil., Cogliati B; University of São Paulo (USP), School of Veterinary Medicine and Animal Science, Department of Pathology, São Paulo, SP, Brazil., Barbisan LF; São Paulo State University (UNESP), Biosciences Institute, Department of Structural and Functional Biology, Botucatu, SP, Brazil., Romualdo GR; São Paulo State University (UNESP), Biosciences Institute, Department of Structural and Functional Biology, Botucatu, SP, Brazil; São Paulo State University (UNESP), Medical School, Department of Pathology, Botucatu, SP, Brazil. Electronic address: guilherme.romualdo@unesp.br.
Jazyk: angličtina
Zdroj: The Journal of steroid biochemistry and molecular biology [J Steroid Biochem Mol Biol] 2022 Jan; Vol. 215, pp. 106022. Date of Electronic Publication: 2021 Nov 10.
DOI: 10.1016/j.jsbmb.2021.106022
Abstrakt: Vitamin D 3 (VD 3 ) deficiency has been associated with increased risk for cirrhosis and hepatocellular carcinoma, a highly incident malignant neoplasia worldwide. On the other hand, VD 3 supplementation has shown some beneficial effects in clinical studies and rodent models of chronic liver disease. However, preventive effects of dietary VD 3 supplementation in cirrhosis-associated hepatocarcinogenesis is still unknow. To investigate this purpose, male Wistar rats submitted to a combined diethylnitrosamine- and thioacetamide-induced model were concomitantly supplemented with VD 3 (5,000 and 10,000 IU/kg diet) for 25 weeks. Liver samples were collected for histological, biochemical and molecular analysis. Serum samples were used to measure 25-hydroxyvitamin D [25(OH)D] and alanine aminotransferase levels. Both VD 3 interventions decreased hepatic collagen deposition and pro-inflammatory p65 protein levels, while increased hepatic antioxidant catalase and glutathione peroxidase activities and serum 25(OH)D, without a clear dose-response effect. Nonetheless, only the highest concentration of VD 3 increased hepatic protein levels of VD receptor, while decreased the number of large preneoplastic glutathione-S-transferase- (>0.5 mm²) and keratin 8/18-positive lesions, as well the multiplicity of hepatocellular adenomas. Moreover, this intervention increased hepatic antioxidant Nrf2 protein levels and glutathione-S-transferase activity. In summary, dietary VD 3 supplementation - in special the highest intervention - showed antifibrotic and antineoplastic properties in chemically-induced cirrhosis-associated hepatocarcinogenesis. The positive modulation of Nrf2 antioxidant axis may be mechanistically involved with these beneficial effects, and may guide future clinical studies.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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