Background/aims: The primary aim of this study was to characterise the blood metabolic profile of hepatocellular carcinoma (HCC) in a rat model, and the secondary aim was to evaluate the effect of the quinolone, norfloxacin on metabolic profiles and exploring the role that gut sterilisation may have on HCC development.
Methods: HCC was induced in 10 Fischer rats by administration of intra-peritoneal diethylnitrosamine (DEN) and oral N-nitrosomorpholine. Plasma was collected upon sacrifice. Five of these rats were concomitantly administered oral norfloxacin. Six Fischer non-treated rats acted as healthy controls. Proton nuclear magnetic resonance (NMR) spectra were acquired using a 600 MHz NMR system.
Results: Control animals were 120 g heavier than diseased counterparts. Proton NMR spectra from diseased rats displayed significant decreases in lipoproteins, unsaturated fatty acids, acetyl-glycoprotein, acetoacetate, and glucose (P ≤ 0.001). Plasma citrate and formate levels were increased (P = 0.02). Norfloxacin appeared to abrogate this effect slightly.
Conclusion: The spectral profiles of plasma in rats with HCC display marked changes with relation to lipid metabolism and cellular turnover. Norfloxacin appears to moderate these metabolic alterations to a small degree.
Keywords: 1-D, one-dimensional; 1H, human proton; CPMG, Carr-Purcell-Meiboom-Gill 3B; DEN, diethylnitrosamine; FID, free induction decay; HCC, hepatocellular carcinoma; HDL, high-density lipoprotein; LDL, low-density lipoprotein; NMOR, N-nitrosomorpholine; NMR spectroscopy; NMR, nuclear magnetic resonance; NOESY, nuclear overhauser effect spectroscopy; PCA, principal components analysis; PLS-DA, partial least squares discriminant analysis; Q2, goodness of prediction; R2, goodness of fit; RD, relaxation delay; RF, radiofrequency; SBP, spontaneous bacterial peritonitis; TLR-4, Toll-like receptor 4; VLDL, very low-density lipoprotein; hepatocellular carcinoma; metabonomics; norfloxacin.