Abstract:
:Chymase stored in mast cells activates matrix metalloproteinase (MMP)-9, which may relate to the progression of sinusoidal obstruction syndrome (SOS). We investigated the preventive effect of a chymase inhibitor, TY-51469, on monocrotaline-induced SOS in hamsters. Hamsters were orally administrated with a single dose of monocrotaline (120 mg/kg) to induce SOS. Treatment with TY-51469 (1 mg/kg per day) or placebo had started 3 days before the monocrotaline administration. Two days after the monocrotaline administration, significant increases in aspartate aminotransferase, alanine aminotransferase and total bilirubin and a significant reduction of albumin were observed in plasma, but their changes were significantly attenuated by treatment with TY-51469. The numerous hepatic necrosis areas were observed in the placebo-treated group, but the ratio of necrotic area to total area in liver had been significantly reduced by treatment with TY-51469. Both chymase activity and MMP-9 level in liver were significantly augmented in the placebo-treated group. Furthermore, tumor necrosis factor (TNF)-α level in liver was also augmented in the placebo-treated group. However, the chymase activity and levels of MMP-9 and TNF-α were significantly attenuated in the TY-51469-treated group. Until 14 days after monocrotaline administration, survival rates in the placebo- and TY-51469-treated groups were 25% and 70%, respectively, and a significant difference was observed. In conclusion, chymase inhibition by TY-51469 may prevent the accelerating of severity in monocrotaline-induced SOS in hamsters.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Masubuchi S,Komeda K,Takai S,Jin D,Tashiro K,Li ZL,Otsuki Y,Okamura H,Hayashi M,Uchiyama Kdoi
10.2174/0929867311320210008subject
Has Abstractpub_date
2013-01-01 00:00:00pages
2723-9issue
21eissn
0929-8673issn
1875-533Xpii
CMC-EPUB-20130315-20journal_volume
20pub_type
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