Role of matrix metalloproteinases in cholestasis and hepatic ischemia/reperfusion injury: A review

Table 2 Synthetic compounds involved in matrix metalloproteinase regulation

Compounds	Mechanism involved	MMPs involved	I/R model	Ref.
Bortezomib	Downregulation of pro-inflammatory (IL-1β, TNF-α and IFN-γ) and pro-fibrotic (VEGF, TGF-β, HGF, bFGF) factors	MMP-2MMP-9	Steatotic orthotopic liver transplant	Tiriveedhi et al[45],Transpl Immunol 2014
KMUP-1 (NO-donor)	Protects from apoptosis-associated free radical generation and pro-inflammation	MMP-9	Hypoxic HepG2 cells	Kuo et al[90], Int J Imm Pharm 2013
CS-1 peptide	Blocks fibronectin α4β1 and decreases the release of pro-inflammatory mediators	MMP-9MT-1-MMP/MMP-14	Cold ischemia	Duarte et al[91],Am J Transpl 2012
CTT peptide	Reduction in TNF-α, IL-1, IL-2 and IFN-γ	MMP-9	Acute small-for-size liver graft	Ma et al[34], Am J Transpl 2010
Cyclic RGD peptide	Depresses inflammatory mediators (IFN-γ)	MMP-9	Steatotic Cold ischemia	Fondevila et al[92],Am J Transpl 2009
ONO-1714	iNOS inhibitor	MMP-9	Warm ischemia	Hamada et al[46], Am J Pathol 2009
RXP409	Inhibitory effects on MMP activity	MMPs	Cold ischemia	Defamie et al[28],Hepatology 2008
Anti-MMP-9	Decrease in expression of TNF-α, IL-2 and IFN-γ	MMP-9	Warm ischemia	Hamada et al[23], Hepatology 2008
CS-1 peptide	Blocks FN α4β1 integrin and its FN ligand	MMP-9	Steatotic orthotopic liver transplant	Moore et al[29], Am J Pathol 2007
ONO-4817	Reduction in TNF-α, IL-1β	MMP-2 and MMP-9	Warm ischemia	Shirahane et al[33],Surgery 2006
NAC	Reduction in free radicals	MMP-9	Warm ischemia	Chen et al[93], Transpl Proc 2005
BB3103	Prostaglandin PGE(1) protection	MMP-2	Cold ischemia	Yang et al[94], Microvasc Res 2002
RXPO3	Protects from necrosis/apoptosis	MMP-3-9-11-13	Warm ischemia	Cursio et al[24], FASEB J 2002

MMP: Matrix metalloproteinase; CS-1: Connecting segment-1; FN: Fibronectin; TNF-α: Tumor necrosis factor; TGF-β: Transforming growth factor β; IFN: Interferon; iNOS: Inducible nitric oxide synthase; IL: Interleukin.