الفهرس 
Targeting hepatic stellate cells using valsartan and imatinib nanomedicine in experimentally induced liver fibrosis in rats
CONTENTSOnly 14 pages are availabe for public view
 |  | from | 271 |  |  |
| | | from | 271 | | |
Abstract
Liver fibrosis is a serious health problem as an intermediate stage in the sequential progression of all chronic liver diseases to cirrhosis then to hepatocellular carcinoma. Despite the growing eagerness to develop anti-fibrotic therapies following deliberating that hepatic fibrosis has tendency to regress, none of the tested anti-fibrotic therapies was approved so far. Hepatic stellate cells (HSCs) are the sole hepatic vitamin A (VA) storage cells besides they are the main regulators for liver fibrosis pathogenesis. A consequence of chronic liver injury is the persistent HSCs activation and trans-differentiation into highly proliferative and matrix-producing myofibroblastes with subsequent loss of the VA storing capacity. These facts paved the way for the idea that HSCs actively-targeted therapy may provide a cure for this reversible morbid condition. The ideal candidate drug for HSCs targeting would be the one which have multiple points of therapeutic intervention, can be easily delivered and is well tolerated. Valsartan and imatinib may represent such candidates; valsartan is an inverse agonist to the over-expressed angiotensin II type1 receptor (AT1R) as well as a partial agonist to the depleted nuclear receptor; peroxisome proliferator-activated receptor gamma (PPAR-Þ) in activated HSCs.On the other hand, being a tyrosine kinase receptor inhibitor, imatinib inhibits platelet-derived growth factor receptor-beta (PDGFR-Ý) and c-Abl. Therefore it inhibits two key profibrotic pathways; PDGF-Ý and transforming growth factor-beta (TGF-Ý). However, efficacy of valsartan on AT1R and PPAR-Þ necessitates high drug permeability which is lacking in valsartan