Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Pharmacology

Hepatic encephalopathy (HE), is a reversible brain dysfunction caused by acute or chronic liver insufficiency, and/or Portosystemic shunt. increased brain levels of Neurosteroids (NS) in HE, have been implicated in pathogenesis of HE. NS potentiate GABAA neuroinhibitory activity, and it directly activate GABAA receptor at higher concentrations. Hence, blockage of NS synthesis by Finasteride, a 5Ü-R inhibitor, which is an essential enzyme in biosynthesis of NS, is postulated as a possible new agent to treat patients with HE, especially in those who didn{u2019}t respond or intolerate the currently used drugs. In the present study, intraperitoneal injection(IP) of rats with thioacetamide (300mg/kg/day) for three days, induced an animal model of HE, due to acute liver damage, type (A) HE, while IP injection of rats with TAA (200mg/kg/dose), twice weekly for 12 weeks, induced a model of HE, due to liver cirrhosis, type (C) HE. Rats were divided into two main groups, group A (type A, HE) and group B (type C, HE), each main group was subdivided into six subgroups (6 rats in each); rats were treated by Finasteride (50mg\kg\day), lactulose (8mg\kg\ day) or their combination, daily for three days for type (A) HE, and for 2 weeks for type (C) HE. Administration of TAA induced neurobehavioral changes in behavioral clinical score, open field test (OFT), and forced swimming test (FST); EEG power spectral density (PSD) changes, characterized by rising in PSD of delta band and reduction in PSD of alpha and theta bands; biochemical changes manifested by derangement in liver function tests and increased in serum ammonia level, and liver and brain histological changes that characterized by hepatic necroinflammation, and brain edema in type A HE and liver fibrosis and Alzheimer type II astrocytosis in in type C HE

Issued also as CD