L-carnitine prevents ammonia-induced cytotoxicity and disturbances in intracellular amino acid levels in human astrocytes
Ting Wang
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
These authors contributed equally to this work.Search for more papers by this authorCorresponding Author
Kazuyuki Suzuki
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
Department of Nutritional Science, Morioka University, Takizawa, Japan
These authors contributed equally to this work.Correspondence
Dr Kazuyuki Suzuki, Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Iwate, Japan.
Email: [email protected]
Search for more papers by this authorKeisuke Kakisaka
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
Search for more papers by this authorMio Onodera
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
Search for more papers by this authorKei Sawara
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
Search for more papers by this authorYasuhiro Takikawa
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
Search for more papers by this authorTing Wang
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
These authors contributed equally to this work.Search for more papers by this authorCorresponding Author
Kazuyuki Suzuki
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
Department of Nutritional Science, Morioka University, Takizawa, Japan
These authors contributed equally to this work.Correspondence
Dr Kazuyuki Suzuki, Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Iwate, Japan.
Email: [email protected]
Search for more papers by this authorKeisuke Kakisaka
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
Search for more papers by this authorMio Onodera
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
Search for more papers by this authorKei Sawara
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
Search for more papers by this authorYasuhiro Takikawa
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
Search for more papers by this authorAbstract
Background and Aim
L-carnitine (L-CA) has been used therapeutically to treat hepatic encephalopathy with hyperammonemia, but the mechanism by which L-CA contributes to ammonia detoxification in the brain is still unclear. Thus, the cytotoxicity and changes in intracellular amino acids (AAs) in astrocytes with hyperammonemia following L-CA administration were studied.
Methods
Human astrocytes were treated with ammonium chloride (NH4Cl), L-CA or a mixture of NH4Cl, and L-CA under defined conditions. Total intracellular reactive oxygen species and lactate dehydrogenase leakage were measured following different treatment periods. The intracellular levels of AAs in astrocytes were determined using metabolomic analysis.
Results
Intracellular total reactive oxygen species and lactate dehydrogenase leakage were significantly increased after treatment with NH4Cl. In contrast, co-treatment with L-CA significantly inhibited the cytotoxic effects of NH4Cl. The intracellular levels of almost all AAs involving glutamine and branched-chain AAs (BCAAs) were significantly increased in the NH4Cl-treated cells compared with in the control cells; these changes in BCAA levels were reduced with L-CA co-treatment. Additionally, the level of 3-methyl-2-oxovaleric acid, which is a metabolite from isoleucine and plays a critical role in neurological damage, was significantly increased in the NH4Cl-treated cells, but this metabolite was significantly decreased with L-CA co-treatment.
Conclusion
L-CA protects human astrocytes from ammonia-induced acute cytotoxic effects and the increased intracellular levels of glutamine and BCAAs.
References
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