NMR-based Metabolomics Analysis of Liver from C57BL/6 Mouse Exposed to Ionizing Radiation

Abstract

The effects of ionizing radiation to human health are of great concern in the field of space exploration and for patients considering radiotherapy. However, to date, the effect of high-dose radiation on metabolism in the liver has not been clearly defined. In this study, 1H nuclear magnetic resonance (NMR)-based metabolomics combined with multivariate data analysis was applied to study the changes of metabolism in the liver of C57BL/6 mouse after whole-body gamma (3.0 and 7.8 Gy) or proton (3.0 Gy) irradiation. Principal component analysis (PCA) and orthogonal projection to latent structures analysis (OPLS) were used for classification and identification of potential biomarkers associated with exposure to gamma and proton radiation. The results show that the radiation exposed groups can be well separated from the control group. Where the same dose was received, the proton exposed group was nevertheless well separated from the gamma-exposed group, indicating that different radiation sources induce different alterations in the metabolic profile. Common among all high-dose gamma and proton exposed groups were the statistically decreased concentrations of choline, O-phosphocholine and trimethylamine N-oxide, while the concentrations of glutamine, glutathione, malate, creatinine, phosphate, betaine and 4-hydroxyphenylacetate were statistically and significantly elevated. Since these altered metabolites are associated with multiple biological pathways, the results suggest that radiation induces abnormality in multiple biological pathways. In particular, metabolites such as 4-hydroxyphenylacetate, betaine, glutamine, choline and trimethylamine N-oxide may be prediagnostic biomarkers candidates for ionizing exposure of the liver.

Urine metabolomics based prediction model approach for radiation exposure

“…In the last few years, many LC-MS metabolomics studies have identified many metabolites associated with radiation exposure 16,21 . However, there are few NMR based studies that have exploited the potential of metabolomics for the identification of potent metabolite markers [22][23][24][25] . Undoubtedly the sensitivity of LC-MS is way ahead of NMR for profiling but the ease of acquisition, identification of metabolites and reproducibility of information in spectrum makes NMR based metabolomics a suitable and comfortable platform in biomarker identification.…”

A comprehensive insight into the metabolic landscape of fruit pulp, peel, and seed in two longan (Dimocarpus longanLour.) varieties

“…O-Phosphocholine acts as an intermediate in phosphatidylcholine synthesis, which is beneficial for memory loss, hepatitis, gallbladder disease, kidney disease, [60] and boosting the immune system. [61] Intake of betaine supplement is complimented with health benefits of improved performance and muscle endurance. [62,63] Besides, we also identified piperidine in pulp tissues with significantly high abundance.…”

Metabolite normalization with local radiotherapy following breast tumor resection

“…Indeed, in accord with the results obtained in the present investigation, RT has been shown to increase the fecal content of α-ketobutyrate, valine, isoleucine, and alanine in cervical cancer patients [ 15 ]. RT also influenced the serum concentrations of 28 metabolites in patients with glyoma [ 16 ], increased the hepatic glutamine concentrations [ 17 ], and significantly modified the saliva metabolome [ 18 ] in mice. Taken together, these data suggest that RT does, indeed, influence metabolism in cancer patients.…”