Introduction The profiling of metabolites, small molecules representing the end points of cellular processes in biofluids, has allowed the detection of novel biomarkers of disease. There are several rat models of hepatocellular carcinoma (HCC), however, there have been no previous reports of 1H NMR spectroscopy plasma metabolic profiling in animal models of HCC. Quinolone antibiotics, such as norfloxacin, are known to reduce the inflammatory component of liver fibrosis potentially reducing end-stage complications. The primary aim of this study was to identify blood metabolic profile biomarkers of HCC in a rat model of HCC and the secondary aim was to evaluate the effect of the norfloxacin on metabolic profiles.
Methods HCC was induced in 10 Fisher rats by administration of intra-peritoneal diethylnitrosamine (DEN) and oral N-nitrosomorpholine (NMOR) and plasma was collected upon sacrifice. Five rats were concomitantly administered oral norfloxacin. Six Fisher non-treated rats acted as healthy controls. Proton NMR spectra were acquired for all samples using a Bruker 600 MHz NMR system and results were analysed by visual comparison and multivariate analysis.
Results Proton NMR spectra from diseased rats displayed significant decreases in lipoproteins, unsaturated fatty acids, N-acetyl-glycoproteins, acetoacetate, and glucose (p≤0.001). Plasma citrate and formate levels were increased (p=0.02). Although animals treated with norfloxacin also developed tumours, background fibrosis and tumour nodularity was less marked than non-antibiotic treated animals. Correspondingly, metabolic profiles from both HCC groups with and without norfloxin were similar in character with the norfloxin treated group showing a slightly weaker set of metabolic alterations.
Conclusion The spectral profiles of plasma in rats with HCC display marked changes with relation to lipid metabolism and cellular turnover which may indicate a fundamental repression of fatty acid oxidation and cancer cachexia. Norfloxacin appears to abrogate these effects slightly. This is the first animal model plasma 1H NMR study to report such findings and may both be translational to human disease and allow the study of the effect metabolic modulation upon HCC progression.
Competing interests None declared.
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