期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 102, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.intimp.2021.108387
关键词
Oridonin; Oxylipin; Acute Liver Injury; D-galactosamine; Lipopolysaccharide
资金
- National Natural Science Foundation of China [81973388, 81600489]
- Marine Economy Development Project of Guangdong Province [GDNRC202152]
- Major Scientific and Technological Projects of Guangdong Province [2019B020202002]
This study investigated the changes in oxylipins in mice with D-GalN/LPS-induced acute liver injury (ALI) and the effects of Oridonin (Ori) on these changes. The results showed that Ori significantly decreased the levels of proinflammatory mediators and altered the oxylipin pathway through COX and LOX pathways, providing a protective effect against ALI.
Background and Purpose: Oridonin (Ori) has been shown to protect against acute liver injury (ALI) induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS). Oxylipins are oxidation products of polyunsaturated fatty acids (PUFAs) and are key proinflammatory mediators. This study aimed to investigate the changes in oxylipins in the livers of mice with D-GalN/LPS-induced ALI and the effects of Ori on these changes. Results: 54 oxylipins in liver tissues were identified and qualitatively and quantitatively analyzed by ultra-performance liquid chromatography-electrospray ionization triple quadrupole mass spectrometry (UPLC-QTRAP/MS/MS). The levels of 12-HETE, 12-HEPE, 14(S)-HDHA, PGE2, dihomo-gamma-linolenic acid and 13-HOTrE in the liver were significantly increased in the D-GalN/LPS-induced ALI group compared with the control group, and the levels of EPA and 7-HDHA were significantly decreased. However, pretreatment with Ori dramatically decreased the levels of 12-HETE, 12-HEPE, 14(S)-HDHA, PGE2 and 13-HOTrE compared with those of the ALI group and induced 7-HDHA and 15-oxoETE. Moreover, Ori reduced the protein levels of COX-1, COX-2, ALOX5, ALOX12 and ALOX15 induced by D-GalN/LPS, indicating that Ori altered oxylipins through the COX and LOX pathways. Conclusions: These results suggest that the protective effect of Ori on ALI is partly mediated by affecting the oxylipin pathway.
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