الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Despite of the scientific progress in the field of liver disorders, hepatic fibrosis still remains a major medical problem with significant morbidity and mortality. The present study was conducted to investigate an improving effect of receptor tyrosine kinases inhibition, mainly growth factor receptors, on liver fibrosis, where the potential anti-fibrotic effect of the multi-targeted receptor tyrosine kinase inhibitor pazopanib was tested on CCl4-induced liver fibrosis model in rats with elucidating possible underlying mechanisms. The model of liver fibrosis: Rats were injected intraperitoneally with 1ml/kg CCl4 (2.5 mL/kg of 40% v/v CCl4 solution in olive oil) twice a week for 8 weeks. To imitate the clinical application of anti-fibrotic drugs, pazopanib administration was started concurrently with CCl4 injection at the beginning of week 5 till the end of week 8. The development of liver fibrosis was assessed mainly by employing hepatic histopathological examination, assessment of liver function and lipid peroxidation biomarkers, assessment of mRNA expressions of hepatic collagen 1 alpha 1 (Col1A1) as a major component of collagen constituting the ECM released by activated HSCs. Treatment with pazopanib attenuated CCl4 induced liver fibrosis progression. This was indicated mainly by decreasing fibrosis score as revealed by examined liver sections histopathologically. The improvement was ensured by lowering elevated liver function biomarkers, reducing lipid peroxidation (low MDA levels). Expressions of Col1A1 was lowered as well So, pazopanib at certain dose level can halt liver fibrosis progression through regulating angiogenesis, modulating inflammatory cytokines, suppressing hepatic stellate cells activity, and inducing their apoptosis.