Silibinin protects mice from T cell-dependent liver injury.
OBJECTIVE
Silibinin is the major pharmacologically active compound of the Silybum marianum fruit extract silymarin. Its well-known hepatoprotective activities are mostly explained by antioxidative properties, inhibition of phosphatidylcholine synthesis or stimulation of hepatic RNA and protein synthesis. Here, we characterized the hepatoprotective potential of silibinin as an immune-response modifier in T cell-dependent hepatitis in vivo.


METHODS
Silibinin was tested in the mouse model of concanavalin A (ConA)-induced, T cell-dependent hepatitis. Liver injury was assessed by quantification of plasma transaminase activities and intrahepatic DNA fragmentation. Plasma cytokine concentrations were determined by enzyme-linked immunosorbent assay (ELISA), intrahepatic cytokine and inducible NO synthase (iNOS) mRNA levels by reverse transcriptase polymerase chain reaction, intrahepatic iNOS expression by immunofluorescent staining, and intrahepatic nuclear factor kappa B (NF-kappaB) activation by electrophoretic mobility shift assay.


RESULTS
Silibinin significantly inhibited ConA-induced liver disease. Silibinin proved to be an immune-response modifier in vivo, inhibiting intrahepatic expression of tumor necrosis factor, interferon-gamma, interleukin (IL)-4, IL-2, and iNOS, and augmenting synthesis of IL-10. In addition, silibinin inhibited intrahepatic activation of NF-kappaB.


CONCLUSIONS
Silibinin, suppressing T cell-dependent liver injury as an immune-response modifier, might be a valuable drug in therapeutic situations in which intrahepatic immunosuppression is required.
Schümann
Jens
J
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Fahrstrasse 17, DE-91054 Erlangen, Germany.
Prockl
Jennifer
J
Kiemer
Alexandra K
AK
Vollmar
Angelika M
AM
Bang
Renate
R
Tiegs
Gisa
G
D000818:Animals; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019610:Cytoprotection; D004790:Enzyme Induction / Q000187:drug effects; D005688:Galactosamine; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008107:Liver Diseases / Q000209:etiology* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D013601:T-Lymphocytes; D014409:Tumor Necrosis Factor-alpha
D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012838:Silymarin; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D000077385:Silybin; D005688:Galactosamine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse