Abstract | BACKGROUND: MATERIAL AND METHODS: Male Wistar rats (n = 20) were orally administered 10 mg/kg/day of OCA (5 days) and subjected to a 60-min ischemia and 60-min reperfusion. Bile, serum and tissue were collected for MMP-2 and MMP-9 activity quantification. The MMP regulator tissue reversion-inducing cysteine rich protein with Kazal motifs (RECK), tissue inhibitor of metalloproteinases (TIMPs), iNOS and biliary levels of LDH, γGT, glucose and ADMA were quantified. RESULTS: In the I/R group, OCA administration reduced MMP-2 and MMP-9 in liver, bile and serum. A downregulation of tissue RECK and TIMPs, observed under I/R, were recovered by OCA. Immunohistochemical staining of hepatic tissue demonstrated that RECK expression is mainly localized in both cholangiocytes and hepatocytes. Hepatic iNOS positively correlated with tissue MMP-2 and MMP-9 activity. Biliary levels of LDH, γGT and glucose were lower in I/R rats treated with OCA; in bile, MMP levels positively correlated with LDH and γGT. CONCLUSION: Thus, OCA administration confers protection to cholangiocytes via downregulation of biliary MMPs in livers submitted to I/R. This event is associated with hepatic RECK- and TIMP-mediated MMP decrease.
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Authors | Andrea Ferrigno, Giuseppina Palladini, Laura Giuseppina Di Pasqua, Clarissa Berardo, Plinio Richelmi, Massimiliano Cadamuro, Luca Fabris, Stefano Perlini, Luciano Adorini, Mariapia Vairetti |
Journal | PloS one
(PLoS One)
Vol. 15
Issue 9
Pg. e0238543
( 2020)
ISSN: 1932-6203 [Electronic] United States |
PMID | 32911524
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Matrix Metalloproteinase Inhibitors
- obeticholic acid
- Chenodeoxycholic Acid
- Matrix Metalloproteinase 2
- Matrix Metalloproteinase 9
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Topics |
- Animals
- Biliary Tract
(drug effects, enzymology, metabolism)
- Chenodeoxycholic Acid
(analogs & derivatives, therapeutic use)
- Liver
(drug effects, enzymology, metabolism)
- Male
- Matrix Metalloproteinase 2
(metabolism)
- Matrix Metalloproteinase 9
(metabolism)
- Matrix Metalloproteinase Inhibitors
(therapeutic use)
- Rats, Wistar
- Reperfusion Injury
(drug therapy, metabolism)
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