Selective inhibition of hepatic collagen accumulation in experimental liver fibrosis in rats by a new prolyl 4-hydroxylase inhibitor

Abstract

Chronic damage to the liver by a variety of causes frequently results in fibrogenesis, the increased deposition of extracellular matrix (ECM) proteins. The main component of the newly formed ECM is collagen.

Inhibition of Prolyl-4-Hydroxylase Ameliorates Chronic Rejection of Mouse Kidney Allografts

“…Similarly, PHI treatment decreases interstitial collagen accumulation and ameliorates clinical cirrhosis in an experimental model of liver fibrosis (41). In our study, there was an improvement in GFR, though with a predominant effect on collagen within the interstitium and tubules, and less so on glomerular lesions.…”

Successful Targeting to Rat Hepatic Stellate Cells Using Albumin Modified with Cyclic Peptides That Recognize the Collagen Type VI Receptor

“…Cellular uptake of pCVI-HSA allows the delivery of antifibrotic drugs that interfere with intracellular processes. Among the drugs of interest are the inhibitors of collagen synthesis such as prolyl-4-hydroxylase inhibitors (37,38), activators of collagenase expression/activation, like pentoxifylline (39), or inhibitors of HSC activation (NFB inhibitors or histone deacetylase inhibitors (40 -42)). …”

Adenosine reverses a preestablished CCl4-induced micronodular cirrhosis through enhancing collagenolytic activity and stimulating hepatocyte cell proliferation in rats

“…3 During cirrhosis, deposition of basement membrane and appearance of continuous capillaries lead to impaired hepatic function, increased portal vein pressure, and reduced hepatic blood flow. 4 Altogether, this makes the cirrhotic process practically irreversible, 5 accompanied with evident functional abnormalities that lead to a significant lethal condition. 6 Cirrhosis is a complex process, for which no proven effective treatment capable of reversing it has been developed.…”

“…Therefore, the aim of this study was to further evaluate the beneficial action of adenosine in a more realistic condition such as reversing a well-established cirrhosis after 10 weeks of CCl 4 administration. This protocol allowed us to assess the effectiveness of adenosine in an experimental condition that resembles more closely the human cirrhotic pathology, and to characterize the antifibrogenic action of adenosine in this experimental model of cirrhosis.…”