| RRC ID |
75805
|
| 著者 |
Kato M, Yamaguchi M, Ooka A, Takahashi R, Suzuki T, Onoda K, Yoshikawa Y, Tsunematsu Y, Sato M, Yoshioka Y, Igarashi M, Hayakawa S, Shoji K, Shoji Y, Ishikawa T, Watanabe K, Miyoshi N.
|
| タイトル |
Non-target GC-MS analyses of fecal VOCs in NASH-hepatocellular carcinoma model STAM mice.
|
| ジャーナル |
Sci Rep
|
| Abstract |
The increased incidence of obesity in the global population has increased the risk of several chronic inflammation-related diseases, including non-alcoholic steatohepatitis (NASH)-hepatocellular carcinoma (HCC). The progression from NASH to HCC involves a virus-independent liver carcinogenic mechanism; however, we currently lack effective treatment and prevention strategies. Several reports have suggested that fecal volatile organic compounds (VOCs) are strongly associated with NASH-HCC; therefore, we explored the biomarkers involved in its pathogenesis and progression. Fecal samples collected from control and NASH-HCC model STAM mice were subjected to headspace autosampler gas chromatography-electron ionization-mass spectrometry. Non-target profiling analysis identified diacetyl (2,3-butandione) as a fecal VOC that characterizes STAM mice. Although fecal diacetyl levels were correlated with the HCC in STAM mice, diacetyl is known as a cytotoxic/tissue-damaging compound rather than genotoxic or mutagenic; therefore, we examined the effect of bioactivity associated with NASH progression. We observed that diacetyl induced several pro-inflammatory molecules, including tumor necrosis factor-α, cyclooxygenase-2, monocyte chemoattractant protein-1, and transforming growth factor-β, in mouse macrophage RAW264.7 and Kupffer KPU5 cells. Additionally, we observed that diacetyl induced α-smooth muscle actin, one of the hallmarks of fibrosis, in an ex vivo cultured hepatic section, but not in in vitro hepatic stellate TWNT-1 cells. These results suggest that diacetyl would be a potential biomarker of fecal VOC in STAM mice, and its ability to trigger the macrophage-derived inflammation and fibrosis may partly contribute to NASH-HCC carcinogenesis.
|
| 巻・号 |
13(1)
|
| ページ |
8924
|
| 公開日 |
2023-6-1
|
| DOI |
10.1038/s41598-023-36091-7
|
| PII |
10.1038/s41598-023-36091-7
|
| PMID |
37264108
|
| PMC |
PMC10235110
|
| MeSH |
Animals
Biomarkers
Carcinogenesis / pathology
Carcinoma, Hepatocellular* / pathology
Diacetyl
Disease Models, Animal
Fibrosis
Gas Chromatography-Mass Spectrometry
Inflammation / pathology
Liver / pathology
Liver Neoplasms* / etiology
Mice
Mice, Inbred C57BL
Non-alcoholic Fatty Liver Disease* / pathology
Volatile Organic Compounds* / pharmacology
|
| IF |
3.998
|
| リソース情報 |
| ヒト・動物細胞 |
RAW 264(RCB0535) |
