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Int. J. Mol. Sci. 2018, 19(9), 2634; https://doi.org/10.3390/ijms19092634

Serum and Hepatic Autofluorescence as a Real-Time Diagnostic Tool for Early Cholestasis Assessment

1
Institute of Molecular Genetics, Italian National Research Council (CNR), Via Abbiategrasso 207, I-27100 Pavia, Italy
2
Department of Biology & Biotechnology, University of Pavia, Via Ferrata 9, I-27100 Pavia, Italy
3
Department of Internal Medicine and Therapeutics, University of Pavia, Via Ferrata 9, I-27100 Pavia, Italy
4
Department of Molecular Medicine, IRCCS San Matteo, University of Pavia, Viale Golgi 5, I-27100 Pavia, Italy
*
Author to whom correspondence should be addressed.
Received: 5 July 2018 / Revised: 17 August 2018 / Accepted: 4 September 2018 / Published: 5 September 2018
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Abstract

While it is well established that various factors can impair the production and flow of bile and lead to cholestatic disease in hepatic and extrahepatic sites, an enhanced assessment of the biomarkers of the underlying pathophysiological mechanisms is still needed to improve early diagnosis and therapeutic strategies. Hence, we investigated fluorescing endogenous biomolecules as possible intrinsic biomarkers of molecular and cellular changes in cholestasis. Spectroscopic autofluorescence (AF) analysis was performed using a fiber optic probe (366 nm excitation), under living conditions and in serum, on the livers of male Wistar rats submitted to bile duct ligation (BDL, 24, 48, and 72 h). Biomarkers of liver injury were assayed biochemically. In the serum, AF analysis distinctly detected increased bilirubin at 24 h BDL. A continuous, significant increase in red-fluorescing porphyrin derivatives indicated the subversion of heme metabolism, consistent with an almost twofold increase in the serum iron at 72 h BDL. In the liver, changes in the AF of NAD(P)H and flavins, as well as lipopigments, indicated the impairment of mitochondrial functionality, oxidative stress, and the accumulation of oxidative products. A serum/hepatic AF profile can be thus proposed as a supportive diagnostic tool for the in situ, real-time study of bio-metabolic alterations in bile duct ligation (BDL) in experimental hepatology, with the potential to eventually translate to clinical diagnosis. View Full-Text
Keywords: BDL model; extrahepatic cholestasis; bilirubin; endogenous porphyrins; energy metabolism; oxidative stress; spectrofluorometry BDL model; extrahepatic cholestasis; bilirubin; endogenous porphyrins; energy metabolism; oxidative stress; spectrofluorometry
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Croce, A.C.; Bottiroli, G.; Di Pasqua, L.G.; Berardo, C.; Siciliano, V.; Rizzo, V.; Vairetti, M.; Ferrigno, A. Serum and Hepatic Autofluorescence as a Real-Time Diagnostic Tool for Early Cholestasis Assessment. Int. J. Mol. Sci. 2018, 19, 2634.

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