Metabolomics Study of the Effects of Zinc Sulfate in Mild Hepatic Encephalopathy

Background: Zinc may play a role in the metabolism of minimal hepatic encephalopathy (MHE). Objective: To investigate the metabolic changes in MHE rats treated by oral zinc sulfate administration. Methods: A total of 24 Sprague-Dawley rats were divided into three subgroups: MHE rats (n=8), ZN rats (MHE treated by zinc sulfate, n=8), and CN rats (sham operation controls, n=8). Morris water maze (MWM) was used to evaluate cognitive and motor functions. The metabolic changes of MHE, ZN, and CN rats were investigated using 1H nuclear magnetic resonance spectroscopy (1H-NMR) based metabolomics. Sparse projection to latent structures discriminant analysis was used to identify the key metabolites in MHE vs. ZN and MHE vs. CN. A diffusion algorithm was used for enrichment analysis of the key metabolomics in MHE. Results: Significant prolonged escape latency of MWM were seen in the MHE rats. Shorter escape latency is shown in ZN rats after zinc supplementation. The 1H-NMR spectroscopy of MHE, ZN and CN rats showed that 47 metabolites were identified for key metabolites analysis. The concentrations of GABA, lactate, alanine, aspartate, glutamate, and glutamine were significantly increased, while that of myo-inositol, taurine, leucine, and isoleucine were significantly decreased in MHE rats. The concentrations of myo-inositol, taurine, glycine, leucine, and isoleucine were significantly increased, while that of lactate, alanine and glutamine were significantly decreased in ZN rats. Conclusions: Zinc sulfate can effectively improve cognitive impairments in MHE rats. Zn played a center role in the nitrogen metabolism of MHE by interfering alanine, glutamate, BACCs metabolisms and TCA circle.