Alterations of glutamine and glutamate levels in patients and rats with hepatocellular carcinoma

Abstract

The alteration of glutamine (Gln) and glutamate (Glu) levels in hepatocellular carcinoma (HCC) has yet to be thoroughly investigated. In this study, 28 HCC patients and 33 healthy people were enrolled. HCC in rats were induced by diethylnitrosamine. Human and rat sera and the extract of rat liver tissues were derivatized with phenylisothiocyanate (PITC) and then separated by an ACQUITY BEH C18 column with 0.1% formic acid and methanol as mobile phase. The UPLC-UV method showed high specificity. Gln and Glu concentrations ranging within 15.6–500 µg/mL showed good linear relationship with the peak area. The average recoveries were 85%–115%. Compared with those in the healthy group, Gln levels in the sera of HCC patients and HCC rats significantly (p < 0.05) decreased, whereas Glu levels increased. In HCC rats, Gln levels in the serum decreased by 36.3%, whereas Gln levels in the liver increased by 33.4%, with no statistical difference in the Gln/Glu ratio. Our results indicated that changes in Gln transporter activity may be closely related to the occurrence and development of HCC, which contributes to the HCC prevention and therapy and thus warrant further study.

Graphical Abstract

Keywords:

• Glutamate metabolism
• glutamine transporter
• hepatocellular carcinoma patients
• hepatocellular carcinoma rats
• phenylisothiocyanate
• precolumn derivatization

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

The work was supported by a grant from the National Natural Science Foundation of China (No. 81560631), The Distinguished Young Scholars Foundation of Jiangxi Province (No. 20162BCB23022), Key Research and development program of Jiangxi Province (No. 20171BBG70086) and Natural Science Foundation of Jiangxi Province (No. 20151BBG70158).