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Conophylline suppresses hepatic stellate cells and attenuates thioacetamide‐induced liver fibrosis in rats
Author(s) -
Kubo Norio,
Saito Rie,
Hamano Kunihisa,
Nagasawa Masahiro,
Aoki Fumiaki,
Takei Izumi,
Umezawa Kazuo,
Kuwano Hiroyuki,
Kojima Itaru
Publication year - 2014
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12328
Subject(s) - hepatic stellate cell , thioacetamide , apoptosis , in vivo , chemistry , tunel assay , fibrosis , hepatic fibrosis , endocrinology , medicine , biology , biochemistry , microbiology and biotechnology
Abstract Background & Aims Conophylline (CnP) is a vinca alkaloid purified from a tropical plant and inhibits activation of pancreatic stellate cells. We investigated the effect of CnP on hepatic stellate cells ( HSC ) in vitro . We also examined whether CnP attenuates hepatic fibrosis in vivo . Method We examined the effect of CnP on the expression of α‐smooth muscle actin (α‐ SMA ) and collagen‐1, DNA synthesis and apoptosis in rat HSC and Lx‐2 cells. We also examined the effect of CnP on hepatic fibrosis induced by thioacetamide (TAA). Results In rat HSC and Lx‐2 cells, CnP reduced the expression of α‐ SMA and collagen‐1. CnP inhibited DNA synthesis induced by serum. CnP also promoted activation of caspase‐3 and induced apoptosis as assessed by DNA ladder formation and TUNEL assay. In contrast, CnP did not induce apoptosis in AML 12 cells. We then examined the effect of CnP on TAA‐induced cirrhosis. In TAA‐treated rats, the surface of the liver was irregular and multiple nodules were observed. Histologically, formation of pseudolobules surrounded by massive fibrous tissues was observed. When CnP was administered together with TAA, the surface of the liver was smooth and liver fibrosis was markedly inhibited. Collagen content was significantly reduced in CnP‐treated liver. Conclusion Conophylline suppresses HSC and induces apoptosis in vitro . CnP also attenuates formation of the liver fibrosis induced by TAA in vivo .