Abstract |
Fumigaclavine C, an alkaloidal metabolite, was produced by Aspergillus fumigatus (strain No. CY018). This study examined the effect of this compound on concanavalin A (Con A)-induced liver injury in mice, a T cell-dependent model of liver damage. Con A administration resulted in severe liver injury, T lymphocyte activation and a strong increment in spleen cell adhesion, as well as in tumour necrosis factor-alpha ( TNF-alpha) production. Against this liver injury, the intraperitoneal administration of fumigaclavine C dose-dependently inhibited the elevation in transaminase activity, TNF-alpha production in serum and the histological changes, including inflammatory infiltration, hepatocyte necrosis and degeneration and Kupffer cell hyperplasia. In addition, this compound in-vitro also inhibited the proliferation of spleen cells induced by Con A, and reduced their IL-2 and TNF-alpha production. Moreover, the intraperitoneal administration of fumigaclavine C inhibited the potential of spleen cells isolated from the liver-injured mice to adhere to fibronectin, laminin and type IV collagen. These results suggest that the improvement of this T cell-mediated liver injury by fumigaclavine C may be related to the inhibition of lymphocyte activation, proliferation and adhesion to extracellular matrices as well as the reduction in TNF-alpha production.
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Authors | Ying Zhao, Junyan Liu, Jun Wang, Lei Wang, Hao Yin, Renxiang Tan, Qiang Xu |
Journal | The Journal of pharmacy and pharmacology
(J Pharm Pharmacol)
Vol. 56
Issue 6
Pg. 775-82
(Jun 2004)
ISSN: 0022-3573 [Print] England |
PMID | 15231043
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2004 The Authors |
Chemical References |
- Alkaloids
- Ergot Alkaloids
- Indole Alkaloids
- Interleukin-2
- Tumor Necrosis Factor-alpha
- fumigaclavine C
- Concanavalin A
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Topics |
- Alkaloids
(pharmacology, therapeutic use)
- Animals
- Aspergillus fumigatus
- Cell Adhesion
(drug effects)
- Cell Division
(drug effects)
- Chemical and Drug Induced Liver Injury
(drug therapy, etiology, pathology)
- Concanavalin A
- Dose-Response Relationship, Drug
- Ergot Alkaloids
- Extracellular Matrix
(physiology)
- Female
- In Vitro Techniques
- Indole Alkaloids
(pharmacology, therapeutic use)
- Injections, Intraperitoneal
- Interleukin-2
(biosynthesis)
- Liver
(drug effects, pathology)
- Male
- Mice
- Spleen
(drug effects, metabolism, pathology)
- T-Lymphocytes
(metabolism, pathology, physiology)
- Tumor Necrosis Factor-alpha
(biosynthesis)
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