Interaction of Manganese and Ammonia in the Brain of Hepatic Encephalopathy Rats

Abstract

Background: Both ammonia and manganese (Mn) play a key role in the pathogenesis of hepatic encephalopathy (HE) and cause similar morphological and functional changes in astrocytes. Objectives: To investigate the interaction between brain Mn and ammonia in HE rats. Methods: Three rat models of minimal HE (MHE), chronic manganism (CHM), and chronic hyperammonemia (CHA) were constructed. A total of 48 Sprague-Dawley rats were divided into one control group (n = 6), MHE groups (n = 18, among which six rats were used to evaluate the MHE model), CHM groups (n = 12), and CHA groups (n = 12). The CHM, CHA, and the rest of MHE rats were randomly divided further into two subgroups, according to the MgSO4 treatment (oral administration of 496 mg/kg/day for seven weeks): MHE-7W and MHE + Mg-7W; CHM-7W and CHM + Mg-7W; and CHA-7W and CHA + Mg-7W, respectively. Rats’ blood ammonia, brain Mn, glutamine synthetase (GS), and glutamine (GLN) levels were measured and compared among groups. Results: Significantly higher brain Mn content in MHE-7W and CHM-7W rats, higher blood ammonia levels, brain GS activity, and GLN content were observed in MHE-7W, CHM-7W, and CHA-7W rats than in control rats. After MgSO4 treatment for seven weeks, significantly lower brain Mn content, blood ammonia levels, and GLN content were observed in MHE, CHM, and CHA rats. Conclusions: Our study showed that brain Mn accumulation could increase brain ammonia levels, while the accumulation of brain ammonia had no effect on the content of brain Mn.