Effect of Blocking Neurosteroids Synthesis on Brain Electrical Activity and behaviour in Animal Models of Type A and Type C Hepatic Encephalopathy

Abstract

Hepatic Encephalopathy (HE) is a brain dysfunction caused by acute or chronic liver insufficiency. Increased brain levels of Neurosteroids (NS) in HE have been implicated in the pathogenesis of HE. Hence, blockage of NS synthesis by Finasteride is postulated as a possible agent to attenuate HE, especially in those who did not respond or were intolerant to the currently used drugs. In the present study, intraperitoneal injection (IP) of rats with thioacetamide for three days induced type (A) HE, while IP injection of rats with TAA twice weekly for 12 weeks induced type (C) HE. Rats were divided into two main groups, group A (type A, HE) and group B (type C, HE), each leading group subdivided into six subgroups (6 rats in each); rats were treated with Finasteride, Lactulose, or their combination, daily for three days for type (A) HE, and two weeks for type (C) HE. Administration of TAA induced neurobehavioral changes in behavioral, clinical score, open field test (OFT), and forced swimming test (FST). Besides, it caused  EEG power spectral density (PSD) changes, derangement in liver function tests, increased serum ammonia level, and brain histological changes. Finasteride had similar effects to Lactulose in ameliorating neurobehavioral, electrophysiological, biochemical, and histopathological changes. The concomitant effect of Finasteride and Lactulose showed better outcomes for all measured parameters and tests.