Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Brain affection is a common symptom of liver insufficiency. This study aimed to evaluate the role of low-dose Þ irradiation (LDR) , morin and pramipexole as a potential therapeutic agents in thioacetamide (TAA)-induced hepatic encephalopathy (HE) in rats. Effects of local and whole body gamma irradiation (0.5 Gy) on rat brain/liver were evaluated following the induction of HE by TAA (200 mg/kg/day/for 3 successive days). Serum activities of aspartate transaminase (AST) and alanine transaminase (ALT) as well as serum ammonia level were assessed.The effect of HE on brain was evaluated through the determination of brain contents of each of malondialdehyde (MDA), reduced glutathione (GSH), tumor necrosis factor-alpha (TNF-Ü) and interleukin-1beta (IL-1Ý) as well as glutathione peroxidase (GPx) activity. Moreover, apoptotic and inflammatory changes in brain and liver tissues were assessed together with alpha-smooth muscle actin (Ü-SMA); liver fibrosis marker. Morin is a flavonoid constituent of many herbs and fruits with anti-inflammatory and antioxidant properties. The hepatic/neuronal supportive effects of morin in an experimental rat model were evaluated following the induction of acute hepatic encephalopathy (HE) by thioacetamide. Also, silymarin was used as a reference standard drug. Pramipexole as a symptomatic treatment was evaluated. Results showed correction of the biochemical parameters, an observation that was supported by the results of the immuno-histochemical examinations. Finally, these findings are therefore indicative that LDR and morin could be of value in the treatment of hepatic encephalopathy induced by TAA, through one or more molecular mechanisms.Pramipexole showed no significant effect on inflammatory markers Pramipexole improved TAA-induced effects on brain GSH content and GPx activity while no effect was noted on MDA brain content

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