Antifibrotic activity of anisodamine in vivo is associated with changed intrahepatic levels of matrix metalloproteinase-2 and its inhibitor tissue inhibitors of metalloproteinases-2 and transforming growth factor beta1 in rats with carbon tetrachloride-induced liver injury.
OBJECTIVE
To investigate the protective effects and the mechanism of anisodamine on deposition of extracellular matrix in experimental liver fibrosis.


METHODS
Experimental liver fibrosis was produced by carbon tetrachloride (CCL(4)). The preventive group was treated for 10 weeks with anisodamine 7.0 mg/kg per day i.p. injection. Two therapeutic groups were treated for 6 weeks by anisodamine 7.0 or 14.0 mg/kg per day i.p. injection. Studies were made at CCL(4) administration on the 10th weekend. Serum biochemical indices and the contents of malondialdehyde (MDA) and hydroxyproline (HYP) in livers were compared. The expression of transforming growth factor-beta1 (TGF-beta1) was observed by immunohistochemistry. The reverse transcription polymerase chain reaction was used to detect the expressions of matrix metalloproteinase-2 (MMP2) and tissue inhibitor of metalloproteinase-2 (TIMP2) mRNA in livers and the ratio of MMP2 and TIMP2 was measured. The proteins of MMP2 in liver were determined by gelatin zymography.


RESULTS
The serum levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase and hyaluronic acid of liver fibrosis rats improved significantly by treatment with anisodamine. The contents of MDA and HYP in liver decreased and the expressions of TGF-beta1 were inhibited by treatment with anisodamine. The levels of MMP2 and TIMP2 mRNA and the protein of MMP2 in livers were significantly reduced in the anisodamine preventive group and therapeutic groups. The expression ratios of MMP2 and TIMP2 mRNA were adjusted in treated groups.


CONCLUSIONS
Anisodamine can inhibit hepatic fibrosis.
Luo
Lin
L
Medical College of Nantong University, Nantong, Jiangsu, China.
Zhou
Ailing
A
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D006820:Hyaluronic Acid / Q000097:blood; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism; D008315:Malondialdehyde / Q000097:blood; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012991:Solanaceous Alkaloids / Q000494:pharmacology*; D013194:Staining and Labeling; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D012991:Solanaceous Alkaloids; D053773:Transforming Growth Factor beta1; C003922:anisodamine; D019716:Tissue Inhibitor of Metalloproteinase-2; D008315:Malondialdehyde; D006820:Hyaluronic Acid; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D020778:Matrix Metalloproteinase 2