Fatty liver oxidative events monitored by autofluorescence optical diagnosis: Comparison between subnormothermic machine perfusion and conventional cold storage preservation

Croce, Anna Cleta; Ferrigno, Andrea; Bertone, Vittorio; Piccolini, Valeria Maria; Berardo, Clarissa; Pasqua, Laura Giuseppina Di; Rizzo, Vittoria; Bottiroli, Giovanni; Vairetti, Mariapia

doi:10.1111/hepr.12779

Cited by 17 publications

(20 citation statements)

References 64 publications

(144 reference statements)

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“…The contribution of fluorescent lipids to liver AF has been validated by measuring the AF spectra from AA as a pure compound in solution and their subsequent use for the fitting analysis of the overall emission of living hepatocytes . The lipid AF fraction has been shown to remain almost stable when rat acute starvation causes overall accumulation of lipids in livers or when livers have been isolated and submitted to experimental preservation and reperfusion . These findings are consistent with the biochemical plasticity of the liver, proposed as a way of preserving a fixed fraction of mobilized lipids against changes in the overall lipid pool induced by external interventions, such as warm ischaemia .…”

Section: Optical Biopsy In Hepatologysupporting

confidence: 57%

“…In hepatology, some interest has been reserved for the AF of PPIX produced following the administration of its precursor 5‐aminolevulinic acid (5‐ALA), for the detection of liver tumour or bile leakage . Another haem‐related product is bilirubin, which has recently emerged as a promising AF biomarker of bile composition and liver functionality . The diagnostic value of bile bilirubin is strengthened by the fact that, besides haemocatheresis, it derives from the catabolism of liver haem proteins, and in particular cytochrome P‐450 which accounts for about 70% of haem turnover in the liver.…”

Section: Endogenous Fluorophoresmentioning

confidence: 99%

“…The balance between the 2 emission regions depends on an interchromophore energy transfer phenomenon, which is favoured by shortening the excitation wavelength and is influenced by bilirubin concentration and microenvironment . The latter includes bile proteins and biliary acids responsible for a blue AF band, causing changes in overall bile AF that reflect bile composition and provide diagnostic information on liver functionality (Supplemental Figure ) …”

Section: Endogenous Fluorophoresmentioning

confidence: 99%

“…[46][47][48] Similar AF changes can reveal alterations in liver energy status and energy production machinery, depending on alterations in nutrients and oxygen supply, and metabolic disorders. [49][50][51][52][53] Porphyrin derivatives fluoresce in the red region at welldefined spectral positions. 54 Protoporphyrin IX (PPIX) belongs to the haem-metabolic/catabolic pathways.…”

Section: Endog Enous Fluorophore Smentioning

confidence: 99%

“…56,57 Another haem-related product is bilirubin, which has recently emerged as a promising AF biomarker of bile composition and liver functionality. 53,[58][59][60] The diagnostic value of bile bilirubin is strengthened by the fact that, besides haemocatheresis, it derives from the catabolism of liver haem proteins, and in particular cytochrome P-450 which accounts for about 70% of haem turnover in the liver.…”

Section: Endog Enous Fluorophore Smentioning

confidence: 99%

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Autofluorescence‐based optical biopsy: An effective diagnostic tool in hepatology

Croce

Ferrigno

Bottiroli

et al. 2018

Liver International

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Autofluorescence emission of liver tissue depends on the presence of endogenous biomolecules able to fluoresce under suitable light excitation. Overall autofluorescence emission contains much information of diagnostic value because it is the sum of individual autofluorescence contributions from fluorophores involved in metabolism, for example, NAD(P)H, flavins, lipofuscins, retinoids, porphyrins, bilirubin and lipids, or in structural architecture, for example, fibrous proteins, in close relationship with normal, altered or diseased conditions of the liver. Since the 1950s, hepatocytes and liver have been historical models to study NAD(P)H and flavins as in situ, real-time autofluorescence biomarkers of energy metabolism and redox state. Later investigations designed to monitor organ responses to ischaemia/reperfusion were able to predict the risk of dysfunction in surgery and transplantation or support the development of procedures to ameliorate the liver outcome. Subsequently, fluorescent fatty acids, lipofuscin-like lipopigments and collagen were characterized as optical biomarkers of liver steatosis, oxidative stress damage, fibrosis and disease progression. Currently, serum AF is being investigated to improve non-invasive optical diagnosis of liver disease. Validation of endogenous fluorophores and in situ discrimination of cancerous from non-cancerous tissue belong to the few studies on liver in human subjects. These reports along with other optical techniques and the huge work performed on animal models suggest many optically based applications in hepatology. Optical diagnosis is currently offering beneficial outcomes in clinical fields ranging from the respiratory and gastrointestinal tracts, to dermatology and ophthalmology. Accordingly, this review aims to promote an effective bench to bedside transfer in hepatology.

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Section: Optical Biopsy In Hepatologysupporting

confidence: 57%

Section: Endogenous Fluorophoresmentioning

confidence: 99%

Section: Endogenous Fluorophoresmentioning

confidence: 99%

Section: Endog Enous Fluorophore Smentioning

confidence: 99%

Section: Endog Enous Fluorophore Smentioning

confidence: 99%

See 3 more Smart Citations

Autofluorescence‐based optical biopsy: An effective diagnostic tool in hepatology

Croce

Ferrigno

Bottiroli

et al. 2018

Liver International

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Deconvolution of the fluorescence spectra measured through a needle probe to assess the functional state of the liver

et al. 2023

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ObjectivesCurrently, one of the most pressing issues for surgeons in the treatment of obstructive jaundice is the ability to assess the functional state of the liver and to detect and determine the degree of liver failure in a timely manner with simple and objective techniques. In this regard, the use of fluorescence spectroscopy method can be considered as one of the ways to improve the informativity of existing diagnostic algorithms in clinical practice and to introduce new diagnostic tools. Thus, the aim of the work was to study in vivo the functional state of liver parenchyma by the method of fluorescence spectroscopy implemented through a needle probe and assess the contribution of the main tissue fluorophores to reveal new diagnostic criteria.Materials and MethodsWe compared data from 20 patients diagnosed with obstructive jaundice and 11 patients without this syndrome. Measurements were performed using a fluorescence spectroscopy method at excitation wavelengths of 365 and 450 nm. Data were collected using a 1 mm fiber optic needle probe. The analysis was based on the comparison of the results of deconvolution with the combinations of Gaussian curves reflecting the contribution of the pure fluorophores in the liver tissues.ResultsThe results showed a statistically significant increase in the contribution of curves reflecting NAD(P)H fluorescence, bilirubin, and flavins in the group of patients with obstructive jaundice. This and the calculated redox ratio values indicated that the energy metabolism of the hepatocytes may have shifted to glycolysis due to hypoxia. An increase in vitamin A fluorescence was also observed. It may also serve as a marker of liver damage, indicating impaired vitamin A mobilization from the liver due to cholestasis.ConclusionsThe results obtained reflect changes associated with shifts in the content of the main fluorophores characterizing hepatocyte dysfunction caused by accumulation of bilirubin and bile acids and after disturbance of oxygen utilization. The contributions of NAD(P)H, flavins, and bilirubin as well as vitamin A can be used for further studies as promising diagnostic and prognostic markers for the course of liver failure. Further work will include collecting fluorescence spectroscopy data in patients with different clinical effects of obstructive jaundice on postoperative clinical outcome after biliary decompression.

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Autofluorescence Spectroscopy for Monitoring Metabolism in Animal Cells and Tissues

Croce

Bottiroli

2017

Methods in Molecular Biology

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Excitation of biological substrates with light at a suitable wavelength can give rise to a light emission in the ultraviolet (UV)-visible, near-infrared (IR) spectral range, called autofluorescence (AF). This is a widespread phenomenon, ascribable to the general presence of biomolecules acting as endogenous fluorophores (EFs) in the organisms of the whole life kingdom. In cytochemistry and histochemistry, AF is often an unwanted signal enhancing the background and affecting in particular the detection of low signals or rare positive labeling spots of exogenous markers. Conversely, AF is increasingly considered as a powerful diagnostic tool because of its role as an intrinsic biomarker directly dependent on the nature, amount, and microenvironment of the EFs, in a strict relationship with metabolic processes and structural organization of cells and tissues. As a consequence, AF carries multiple information that can be decrypted by a proper analysis of the overall emission signal, allowing the characterization and monitoring of cell metabolism in situ, in real time and in the absence of perturbation from exogenous markers. In the animal kingdom, AF studies at the cellular level take advantage of the essential presence of NAD(P)H and flavins, primarily acting as coenzymes at multiple steps of common metabolic pathways for energy production, reductive biosynthesis and antioxidant defense. Additional EFs such as vitamin A, porphyrins, lipofuscins, proteins, and neuromediators can be detected in different kinds of cells and bulk tissues, and can be exploited as photophysical biomarkers of specific normal or altered morphofunctional properties, from the retinoid storage in the liver to aging processes, metabolic disorders or cell transformation processes. The AF phenomenon involves all living system, and literature reports numerous investigations and diagnostic applications of AF, taking advantage of continuously developing self-assembled or commercial instrumentation and measuring procedures, making almost impossible to provide their comprehensive description. Therefore a brief summary of the history of AF observations and of the development of measuring systems is provided, along with a description of the most common EFs and their metabolic significance. From our direct experience, examples of AF imaging and microspectrofluorometric procedures performed under a single excitation in the near-UV range for cell and tissue metabolism studies are then reported.

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Fatty liver oxidative events monitored by autofluorescence optical diagnosis: Comparison between subnormothermic machine perfusion and conventional cold storage preservation

Cited by 17 publications

References 64 publications

Autofluorescence‐based optical biopsy: An effective diagnostic tool in hepatology

Autofluorescence‐based optical biopsy: An effective diagnostic tool in hepatology

Deconvolution of the fluorescence spectra measured through a needle probe to assess the functional state of the liver

Autofluorescence Spectroscopy for Monitoring Metabolism in Animal Cells and Tissues

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