Oral magnesium sulphate administration in rats with minimal hepatic encephalopathy: NMR-based metabolic
Xue-Fei Liu1, Jin-Jin Lu1,2, Ying Li1
1Department of Radiology, Jinshan Hospital, Fudan University, Shanghai, China
Objective:
To investigate the metabolic changes in rats with minimal hepatic encephalopathy (MHE) treated with oral magnesium sulphate administration.
Materials And Methods:
A total of 30 Sprague-Dawley rats were divided into a control group and MHE group (further divided into an MHE group and an MHE-Mg group treated with oral administration of 124 mg/kg/day magnesium sulphate). Morris water maze (MWM), Y maze and narrow beam walking (NBW) were used to evaluate cognitive and motor functions. Brain manganese and magnesium content were measured. The metabolic changes in rats with MHE were investigated using hydrogen-nuclear magnetic resonance. Metabolomic signatures were identified with enrichment and pathway analysis.
Results:
A significantly decreased number of entries into the MWM within the range of interest, longer latency and total time during NBW, and higher brain manganese content were found in rats with MHE. After magnesium sulphate treatment, the rats with MHE had better behavioural performance and lower brain manganese content. The 25 and 26 metabolomic signatures were identified in the cortex and striatum of rats with MHE. The pathway analysis revealed alanine, aspartate and glutamate metabolism as the major abnormal metabolic pathways associated with these metabolomic signatures.
Conclusion:
Alanine, aspartate and glutamate metabolism are major abnormal metabolic pathways in rats with MHE, which could be restored by magnesium sulphate treatment.
Insights
Magnesium sulphate treatment improved cognitive and motor functions in rats with minimal hepatic encephalopathy (MHE). This study identified key metabolic pathway alterations in MHE, particularly in alanine, aspartate, and glutamate metabolism.
Area of Science:
- Biochemistry
- Neuroscience
- Pharmacology
Background:
- Minimal hepatic encephalopathy (MHE) is a subclinical stage of liver dysfunction impacting cognitive and motor functions.
- Metabolic alterations in the brain are implicated in the pathophysiology of MHE.
- Oral magnesium sulphate is a potential therapeutic agent for MHE.
Purpose of the Study:
- To investigate the metabolic changes in rats with MHE.
- To evaluate the therapeutic effect of oral magnesium sulphate on MHE in rats.
- To identify specific metabolic pathways affected in MHE.
Main Methods:
- 30 Sprague-Dawley rats were divided into control, MHE, and MHE treated with magnesium sulphate groups.
- Cognitive and motor functions were assessed using Morris water maze, Y maze, and narrow beam walking tests.
- Brain manganese and magnesium levels were measured, and metabolic changes were analyzed using hydrogen-nuclear magnetic resonance and pathway analysis.
Main Results:
- MHE rats exhibited impaired cognitive and motor functions and increased brain manganese levels.
- Magnesium sulphate treatment improved behavioral performance and reduced brain manganese content in MHE rats.
- Significant metabolomic signatures were identified in the cortex and striatum, with alanine, aspartate, and glutamate metabolism highlighted as major affected pathways.
Conclusions:
- Alanine, aspartate, and glutamate metabolism are critically altered in MHE.
- Magnesium sulphate administration shows promise in restoring these metabolic pathways and improving MHE symptoms.
