Biosensor for Hepatocellular Injury Corresponds to Experimental Scoring of Hepatosplenic Schistosomiasis in Mice

Sombetzki, Martina; Koslowski, Nicole; Doß, Sandra; Loebermann, Micha; Trauner, Michael; Reisinger, Emil C.; Sauer, Martin

doi:10.1155/2016/1567254

Cited by 11 publications

(15 citation statements)

References 22 publications

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“…The panel of assays to study hepatocyte function and viability employed in this study has been previously patented for the early detection of patients endangered for the development of liver dysfunction during sepsis [ 15 , 16 ]. Further standardization was done by the employment of the panel for screening purposes during extracorporeal treatments and for an experimental model of liver dysfunction in Schistosoma infections [ 30 , 31 ]. It utilizes the human hepatocellular carcinoma cell line HepG2/C3A, a well-characterized subclone of the hepatoma-derived HepG2 cell line often used for toxicological screening [ 32 – 34 ].…”

Section: Discussionmentioning

confidence: 99%

Procalcitonin Impairs Liver Cell Viability and Function In Vitro: A Potential New Mechanism of Liver Dysfunction and Failure during Sepsis?

Sauer

Doß

Ehler

et al. 2017

BioMed Research International

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Purpose. Liver dysfunction and failure are severe complications of sepsis and result in poor outcome and increased mortality. The underlying pathologic mechanisms of hepatocyte dysfunction and necrosis during sepsis are only incompletely understood. Here, we investigated whether procalcitonin, a biomarker of sepsis, modulates liver cell function and viability. Materials and Methods. Employing a previously characterized and patented biosensor system evaluating hepatocyte toxicity in vitro, human hepatocellular carcinoma cells (HepG2/C3A) were exposed to 0.01–50 ng/mL procalcitonin for 2 × 72 h and evaluated for proliferation, necrosis, metabolic activity, cellular integrity, microalbumin synthesis, and detoxification capacity. Acetaminophen served as positive control. For further standardization, procalcitonin effects were confirmed in a cellular toxicology assay panel employing L929 fibroblasts. Data were analyzed using ANOVA/Tukey's test. Results. Already at concentrations as low as 0.25 ng/mL, procalcitonin induced HepG2/C3A necrosis (P < 0.05) and reduced metabolic activity, cellular integrity, synthesis, and detoxification capacity (all P < 0.001). Comparable effects were obtained employing L929 fibroblasts. Conclusion. We provide evidence for procalcitonin to directly impair function and viability of human hepatocytes and exert general cytotoxicity in vitro. Therapeutical targeting of procalcitonin could thus display a novel approach to reduce incidence of liver dysfunction and failure during sepsis and lower morbidity and mortality of septic patients.

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Section: Discussionmentioning

confidence: 99%

Procalcitonin Impairs Liver Cell Viability and Function In Vitro: A Potential New Mechanism of Liver Dysfunction and Failure during Sepsis?

Sauer

Doß

Ehler

et al. 2017

BioMed Research International

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“…We paid special attention to the different, widely spread infection intensities in order to investigate whether these differences can be quantified by MRI or PET/CT. We have used the system of 25, 50 and 100 cercariae in the past to analyze mild, moderate and severe clinical picture 34 . However, histological analyses of the granuloma sizes and collagen fibers within the livers using HE and SR staining revealed comparable results.…”

Section: Discussionmentioning

confidence: 99%

“…S. mansoni cercariae were obtained by mass shedding of 5-10 infected B. glabrata after day light exposure. With our experimental design we aim to investigate three widely differing infection intensities and degrees of liver damage 34 . Each mouse was exposed to parasites by sitting in a water bath enriched with 25 (n = 4, light infection), 50 (n = 5, moderate infection) and 100 (n = 5, high infection) S. mansoni cercariae for 90 min.…”

Section: Schistosoma Mansoni Infection Model and Study Design Schistmentioning

confidence: 99%

Anatomical MRI and [18F]FDG PET/CT imaging of Schistosoma mansoni in a NMRI mouse model

Lindner

Stenzel

Koslowski

et al. 2020

Sci Rep

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Schistosomiasis represents one of the most devastating worm parasitosis in the world. Current diagnostic methods are insufficient to determine the infection grade and the disease related organ damage. We herein investigated whether discrimination of infection grade and its correlation to liver damage could be accurately performed by multimodal imaging in a mouse model of Schistosoma mansoni infection. Therefore, groups of uninfected and infected mice underwent MRI and [18F]FDG PET/CT imaging. Anatomical MRI images were used for liver volumetry and for quantification of hepatic granulomas. For PET/CT images a volume of interest based analyses were employed to calculate the [18F]FDG uptake in liver, portal vein, spleen and abdomen. Herein, we demonstrate that the combined use of [18F]FDG-PET/CT and MRI represents an appropriate diagnostic tool for Schistosoma mansoni infection, but fails to discriminate the infection grade and the linked organ damage. Only the splenic [18F]FDG uptake in the 25 cercariae group (5.68 ± 0.90%ID/cc) and 50 cercariae group (4.98 ± 1.43%ID/cc) was significantly higher compared to the control group (2.13 ± 0.69%ID/cc). Nevertheless, future multimodal imaging studies with new radiopharmaceuticals could build a highly sensitive and specific basis for the diagnosis and evaluation of organ damage of schistosomiasis.

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“…The antimycotics were tested in an established microtiter plate assay for screening of hepatotoxicity [ 19 – 22 ]. HepG2/C3A cells were seeded in 24-well plates at 500.000 cells/well and were incubated for 72 hours with the different drugs in 1 ml medium or heparinized plasma from healthy volunteers (pooled plasma).…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, therapeutic drug monitoring (TDM), in combination with clinical assessment of the therapeutic effect, may help to optimize treatment results [ 18 ]. The aim of the presented study was to determine the hepatotoxicity of antimycotics used for systemic infections with human hepatocytes (HepG2/C3A) in an established in vitro cytotoxicity screening model [ 19 – 22 ].…”

Section: Introductionmentioning

confidence: 99%

Hepatotoxicity of Antimycotics Used for Invasive Fungal Infections: In Vitro Results

Doß

Potschka

Mitzner

et al. 2017

BioMed Research International

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Purpose. Drug-induced liver injury (DILI) is the most common cause of liver injury and a serious clinical problem; antimycotics are involved in approximately 3% of all DILI cases. The hepatotoxicity of many drugs, including the antimycotics, is poorly screened in human models. Methods. In a standardized assay the cytotoxicity on hepatocytes of different concentrations (Cmax, 5x Cmax, and 10x Cmax) of the antimycotics used for systemic infections was tested. Anidulafungin (ANI), liposomal amphotericerin B (L-AmB), caspofungin (CASPO), fluconazole (FLUCO), and voriconazole (VORI) were incubated with HepG2/C3A cells. After incubation, the viability of cells (XTT test, LDH release, trypan blue staining), the synthesis of albumin, the cytochrome 1A2 activity, and the cell death (DNA fragmentation) were determined. Kruskal-Wallis and Mann–Whitney tests were used for statistical analyses. Results. L-AmB, ANI, and CASPO showed a mild hepatotoxicity in the Cmax concentrations. Higher concentrations of anidulafungin led to a severe impairment of hepatocyte viability and function. The azoles FLUCO and VORI had a higher hepatotoxic potential in all concentrations. Conclusion. Antimycotics, especially azoles, used for systemic infections should be given with caution in patient with liver insufficiency or liver failure or high risk for this; therefore, therapeutic drug monitoring should be used. Further studies with this approach are encouraged.

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Biosensor for Hepatocellular Injury Corresponds to Experimental Scoring of Hepatosplenic Schistosomiasis in Mice

Cited by 11 publications

References 22 publications

Procalcitonin Impairs Liver Cell Viability and Function In Vitro: A Potential New Mechanism of Liver Dysfunction and Failure during Sepsis?

Procalcitonin Impairs Liver Cell Viability and Function In Vitro: A Potential New Mechanism of Liver Dysfunction and Failure during Sepsis?

Anatomical MRI and [18F]FDG PET/CT imaging of Schistosoma mansoni in a NMRI mouse model

Hepatotoxicity of Antimycotics Used for Invasive Fungal Infections: In Vitro Results

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