[Suppressive effect of tritoqualine (TRQ) on the acceleration of fibrosis in the liver].
Liver cirrhosis was induced by consecutive CCl4-treatment of rats (0.5 ml/kg, s.c., 2 times/week) to investigate the effect of TRQ on the acceleration of fibrosis in the liver. An increase of hydroxyproline content in the liver of rats began 12 weeks after the CCl4 treatment and a 1.9-fold increase was observed at week 14 compared with non-CCl4 treated rats. Histamine in the liver increased about 2 times at week 14. Increased numbers of mast cells were seen in the area of proliferated collagen fiber in the liver under microscopic observation, and also a good correlation was recognized between the number of mast cells and the progression of fibrosis. An administration of TRQ to the rats for 2 weeks from week 13 resulted in significant suppression of both the increase in hydroxyproline and histamine in the liver dose-dependently compared with the CCl4 control group. Both progression of collagen and increase in mast cell numbers were also suppressed by TRQ dose-dependently under histopathological observation; at the same time the decrease in mast cells was recognized to correspond to the decrease in hydroxyproline and histamine in the liver. Thus, it was suggested that increased mast cells participated in the biosynthesis of collagen. Though the elevated serum transaminases, alkaline phosphatase and leucine amino peptidase were also suppressed by TRQ administration, the protein biosynthesis activity of the liver and lowered serum total cholesterol were not improved as much as the other parameters. From these results, it was shown that TRQ was especially and remarkably effective in suppressing the acceleration of fibrosis, and one of the pharmacological mechanisms of this action may be ascribed to the inhibitory effect of TRQ on the activation of mast cells by some stimulants.
K
K
Umezu
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S
Yuasa
A
A
Sudoh
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M
Inagaki
D000818:Animals; D002251:Carbon Tetrachloride / Q000037:antagonists & inhibitors; D003094:Collagen / Q000378:metabolism; D006632:Histamine / Q000032:analysis; D007546:Isoquinolines / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008407:Mast Cells / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains
D007546:Isoquinolines; D006632:Histamine; D003094:Collagen; D002251:Carbon Tetrachloride; C003722:tritoqualine