Abstract:

Objective  To investigate the inhibitory role of ebselen on hepatic encephalopathy (HE) of rats and explore the probable mechanism. Methods  40 male Wistar rats were divided into 4 groups randomly: blank control group (Ⅰ), HE model group (Ⅱ), ebselen treated group (Ⅲ) and solvent control group (Ⅳ). All the groups were treated with thioacetamide (TAA) by intraper-itoneal injection except group Ⅰ (treated with normal saline) to manufacture the model of HE. Then the 4 groups were intragastrically administered with normal saline (Ⅰ, Ⅱ), ebselen (Ⅲ) and dimethyl sulfoxide (DMSO) (Ⅳ) respectively for 1 week untill the symptoms of HE changed. The rats were sacrificed to collect blood for the following detection of 3-nitrotyrosine, alanine transarninase, malondialdehyde and superoxide dismutase. Pathological sections were made to observe the liver changes. Results  The development of HE was slower in group Ⅲ  than in groups Ⅱ and Ⅳ; and the differences of serum markers between groups Ⅲ and Ⅱ, and between groups Ⅲ and Ⅳ were significant (P<0.05), while the difference between groups Ⅲ andⅠwere not obvious (P>0.05). Conclusions  The results suggest that ebselen probably has inhibitory effect on HE of rats induced by TAA and can delay the development of HE. The mechanism may be related to the capability of ebselen, which can clear peroxynitrite anion and inhibit the nitration of tyrosine.

Key words: Ebselen; Hepatic encephalopathy; 3-nitrotyrosine