日本薬理学会年会要旨集
Online ISSN : 2435-4953
WCP2018 (The 18th World Congress of Basic and Clinical Pharmacology)
セッションID: WCP2018_PO3-4-27
会議情報

Poster session
Lansoprazole prevents the progression of liver fibrosis in nonalcoholic steatohepatitis model rats
Toshio NishiYuta YamamotoNaoko YamagishiMikitaka IguchiHideyuki TamaiTakao ItoYoshihiro TsuruoMasao IchinoseMasayuki KitanoTakashi Ueyama
著者情報
キーワード: NASH, Nrf2
会議録・要旨集 オープンアクセス

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Background: Lansoprazole increased the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which is a transcription factor, and their down-stream genes, including heme oxygenase 1 (HO-1) gene, which encodes an anti-oxidant protein in rat livers. Lansoprazole also indicated hepatoprotection in a drug-induced hepatitis animal model in our previous study. We examined whether the hepatoprotection inhibited the progression of nonalcoholic steatohepatitis (NASH) using NASH model rats.

Methods: Six-week-old rats were given a normal chow or a choline-deficient amino acid-defined (CDAA) diet to prepared NASH model rats. The groups given a CDAA diet for 5 weeks was subcutaneously administered vehicle or lansoprazole suspension for 4 weeks following the week after the experiment was started.

Results: The bridging fibrosis was observed in the livers of almost all NASH model rats (6/7), but it was not always observed in that of NASH model rats (1/7) constitutively given lansoprazole. The serum aspartate aminotransferase level elevated by the CDAA diet was significantly decreased by lansoprazole administration. Lansoprazole also increased the expression of Nrf2 but not HO-1 in the liver of NASH model rats. Lansoprazole did not change the expression of transforming growth factor (Tgf) beta 1 related to hepatic fibrosis, but it decreased the level of activated TGF-beta protein. Furthermore, the expression of interleukin-6 gene and protein was decreased.

Conclusions: Lansoprazole might inhibit the progression of NASH, at least in the early stages, in CDAA diet-induced NASH model rats. Their mechanisms might be associated with the cytokines but not the anti-oxidant proteins.

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© 2018 The Authors(s)
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