الفهرس 
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Abstract
Acetaminophen (APAP) was widely utilized as painkiller. APAP is safe at therapeutic levels but can cause significant hepatotoxicity at doses greater than 4 g/day . The aim of the present study was to test whether HIF-1 activation is involved in APAP-induced toxicity in mice, and if so, could targeting HIF-1activation limit the deleterious manifestation of APAP-induced toxicity.In this study, the potential role of nilotinib (5&10 mg/kg) and acriflavin (4&8 mg/kg) pretreatments against acetaminophen-induced liver injurywas investigated.Our findings suggested that pretreatment with nilotinib and acriflavin partially enhanced the observed effects associated with paracetamol toxicity. This effect was observed mainly in terms of improving the activities of enzymes (AST, ALT, ALP, LDH, gamma-GT and total bilirubin). It also recorded a significant decrease in (MDA) and a rise in (SOD and GSH). A decrease in the expression of hypoxia-inducible factor-1 alpha in the liver was also observed. Their administration also improves histopathological changes in liver tissue and decrease the expression of VEGF.