Mohamed I F Shariff1, Joshua M Tognarelli1, Matthew R Lewis2, Elizabeth J Want2, Fatma El Zahra Mohamed3, Nimzing G Ladep4, Mary M E Crossey4, Shahid A Khan1, Rajiv Jalan5, Elaine Holmes2, Simon D Taylor-Robinson1. 1. Liver Unit, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London, United Kingdom. 2. Department of Surgery and Cancer, Imperial College London, Division of Computational and Systems Medicine, London SW7 2AZ, United Kingdom. 3. Pathology Department, Minia University, Minia, Egypt. 4. Liver Unit, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London, United Kingdom; Department of Surgery and Cancer, Imperial College London, Division of Computational and Systems Medicine, London SW7 2AZ, United Kingdom. 5. Department of Medicine, University College London, Royal Free Hospital, London NW3 2QG, United Kingdom.
Abstract
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.
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.
Entities:
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
Authors: J M Llovet; R Bartolí; R Planas; B Viñado; J Pérez; E Cabré; J Arnal; I Ojanguren; V Ausina; M A Gassull Journal: Hepatology Date: 1996-04 Impact factor: 17.425
Authors: Olaf Beckonert; Hector C Keun; Timothy M D Ebbels; Jacob Bundy; Elaine Holmes; John C Lindon; Jeremy K Nicholson Journal: Nat Protoc Date: 2007 Impact factor: 13.491
Authors: Anne Rabiller; Hilario Nunes; Didier Lebrec; Khalid A Tazi; Myriam Wartski; Elisabeth Dulmet; Jean-Marie Libert; Christine Mougeot; Richard Moreau; Michel Mazmanian; Marc Humbert; Philippe Hervé Journal: Am J Respir Crit Care Med Date: 2002-08-15 Impact factor: 21.405
Authors: David S Wishart; Dan Tzur; Craig Knox; Roman Eisner; An Chi Guo; Nelson Young; Dean Cheng; Kevin Jewell; David Arndt; Summit Sawhney; Chris Fung; Lisa Nikolai; Mike Lewis; Marie-Aude Coutouly; Ian Forsythe; Peter Tang; Savita Shrivastava; Kevin Jeroncic; Paul Stothard; Godwin Amegbey; David Block; David D Hau; James Wagner; Jessica Miniaci; Melisa Clements; Mulu Gebremedhin; Natalie Guo; Ying Zhang; Gavin E Duggan; Glen D Macinnis; Alim M Weljie; Reza Dowlatabadi; Fiona Bamforth; Derrick Clive; Russ Greiner; Liang Li; Tom Marrie; Brian D Sykes; Hans J Vogel; Lori Querengesser Journal: Nucleic Acids Res Date: 2007-01 Impact factor: 16.971
Authors: H Akkiz; B I Carr; V Guerra; R Donghia; K Yalçın; U Karaoğullarından; E Altıntaş; A Özakyol; H Şimşek; H Y Balaban; A Balkan; A Uyanıkoğlu; N Ekin; A Delik Journal: J Transl Sci Date: 2020-09-16
Authors: Nahum Méndez-Sánchez; Alejandro Valencia-Rodriguez; Alfonso Vera-Barajas; Ludovico Abenavoli; Emidio Scarpellini; Guadalupe Ponciano-Rodriguez; David Q-H Wang Journal: Hepatoma Res Date: 2020-02-20
Authors: Ji Ye Hyun; Seul Ki Kim; Sang Jun Yoon; Su Been Lee; Jin-Ju Jeong; Haripriya Gupta; Satya Priya Sharma; Ki Kwong Oh; Sung-Min Won; Goo Hyun Kwon; Min Gi Cha; Dong Joon Kim; Raja Ganesan; Ki Tae Suk Journal: Int J Mol Sci Date: 2022-08-06 Impact factor: 6.208