Impaired cell functions of hepatocytes incubated with plasma of septic patients

Sauer, Martin; Haubner, Cristof; Mencke, Thomas; Nöldge-Schomburg, Gabriele; Mitzner, Steffen; Altrichter, Jens; Stange, Jan

doi:10.1007/s00011-012-0451-9

Cited by 15 publications

(19 citation statements)

References 44 publications

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“…To distinguish between moderate (50 cercariae) and heavy (100 cercariae) S. mansoni infection we performed a cell based analysis of hepatotoxicity in the HepG2/C3A hepatocyte cell line [ 9 , 10 ]. The incubation with plasma of the three experimental groups (naive, 50 cercariae, and 100 cercariae) led to a significant impairment of cell viability in the infected groups only.…”

Section: Discussionmentioning

confidence: 99%

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

Sombetzki

Koslowski

Doß

et al. 2016

BioMed Research International

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Severe hepatosplenic injury of mansonian schistosomiasis is caused by Th2 mediated granulomatous response against parasite eggs entrapped within the periportal tissue. Subsequent fibrotic scarring and deformation/sclerosing of intrahepatic portal veins lead to portal hypertension, ascites, and oesophageal varices. The murine model of Schistosoma mansoni (S. mansoni) infection is suitable to establish the severe hepatosplenic injury of disease within a reasonable time scale for the development of novel antifibrotic or anti-infective strategies against S. mansoni infection. The drawback of the murine model is that the material prepared for complex analysis of egg burden, granuloma size, hepatic inflammation, and fibrosis is limited due to small amounts of liver tissue and blood samples. The objective of our study was the implementation of a macroscopic scoring system for mice livers to determine infection-related organ alterations of S. mansoni infection. In addition, an in vitro biosensor system based on the detection of hepatocellular injury in HepG2/C3A cells following incubation with serum of moderately (50 S. mansoni cercariae) and heavily (100 S. mansoni cercariae) infected mice affirmed the value of our scoring system. Therefore, our score represents a valuable tool in experimental schistosomiasis to assess severity of hepatosplenic schistosomiasis and reduce animal numbers by saving precious tissue samples.

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Section: Discussionmentioning

confidence: 99%

“…Two mL heparinized plasma was drawn from all three experimental groups for testing with the in vitro hepatotoxicity test [ 9 , 10 ]. To determine the toxicity of animal plasma the human hepatocytes cell line HepG2/C3A obtained from the American Type Culture Collection (ATCC CRL-10741) was used.…”

Section: Methodsmentioning

confidence: 99%

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

Sombetzki

Koslowski

Doß

et al. 2016

BioMed Research International

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“…The HepG2/C3A cells are used as a model cell line for studying parenchymal biosynthesis (Knowles, Howe & Aden, 1980;Zannis et al, 1981;Nibourg et al, 2012) and screening for cytotoxicity of drug compounds for side effects involving liver injury (Gaskell et al, 2016;Doß et al, 2017). The cell line has also been considered for testing clinical samples in screening for diseases (Sauer et al, 2012;Sauer et al, 2018). Furthermore, the HepG2/C3A cell line has been used in clinical trials as a therapeutic in an extracorporeal bioartificial liver device (Nibourg et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Albumin promotes proliferation of G1 arrested serum starved hepatocellular carcinoma cells

Ibrahim

Stange

Dominik

et al. 2020

PeerJ

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Albumin is the most abundant plasma protein and functions as a transport molecule that continuously interacts with various cell types. Because of these properties, albumin has been exploited by the pharmaceutical industry to improve drug delivery into target cells. The immediate effects of albumin on cells, however, require further understanding. The cell interacting properties and pharmaceutical applications of albumin incentivises continual research into the immediate effects of albumin on cells. The HepG2/C3A hepatocellular carcinoma cell line is used as a model for studying cancer pathology as well as liver biosynthesis and cellular responses to drugs. Here we investigated the direct effect of purified albumin on HepG2/C3A cell proliferation in the absence of serum, growth factors and other serum originating albumin bound molecules. We observed that the reduced cell counts in serum starved HepG2/C3A cultures were increased by the inclusion of albumin. Cell cycle analysis demonstrated that the percentage of cells in G1 phase during serum starvation was reduced from 86.4 ± 2.3% to 78.3 ± 3.2% by the inclusion of albumin whereas the percentage of cells in S phase was increased from 6.5 ± 1.5% to 14.3 ± 3.6%. A significant reduction in the cell cycle inhibitor protein, P21, accompanied the changes in the proportions of cell cycle phases upon treatment with albumin. We have also observed that the levels of dead cells determined by DNA fragmentation and membrane permeabilization caused by serum starvation (TUNEL: 16.6 ± 7.2%, ethidium bromide: 13.8 ± 4.8%) were not significantly altered by the inclusion of albumin (11.6 ± 10.2%, ethidium bromide: 16.9 ± 8.9%). Therefore, the increase in cell number was mainly caused by albumin promoting proliferation rather than protection against cell death. These primary findings demonstrate that albumin has immediate effects on HepG2/C3A hepatocellular carcinoma cells. These effects should be taken into consideration when studying the effects of albumin bound drugs or pathological ligands bound to albumin on HepG2/C3A cells.

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“…The HepG2/C3A cells are used as a model cell line for studying parenchymal biosynthesis (Knowles, Howe & Aden, 1980;Zannis et al, 1981;Nibourg et al, 2012) and screening for cytotoxicity of drug compounds for side effects involving liver injury (Gaskell et al, 2016;Doß et al, 2017). The cell line has also been considered for testing clinical samples in screening for diseases (Sauer et al, 2012(Sauer et al, , 2018. Furthermore, the HepG2/C3A cell line has been used in clinical trials as a therapeutic in an extracorporeal bioartificial liver device (Nibourg et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Peer Review #2 of "Albumin promotes proliferation of G1 arrested serum starved hepatocellular carcinoma cells (v0.1)"

2020

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Albumin is the most abundant plasma protein and functions as a transport molecule that continuously interacts with various cell types. Because of these properties, albumin has been exploited by the pharmaceutical industry to improve drug delivery into target cells. The immediate effects of albumin on cells however require further understanding. The cell interacting properties and pharmaceutical applications of albumin incentivises continual research into the immediate effects of albumin on cells. The HepG2/C3A hepatocellular carcinoma cell line is used as a model for studying cancer pathology as well as liver biosynthesis and cellular responses to drugs. Here we investigated the direct effect of purified albumin on HepG2/C3A cell proliferation in the absence of serum, growth factors and other serum originating albumin bound molecules. We observed that the reduced cell counts in serum starved HepG2/C3A cultures were increased by the inclusion of albumin. Cell cycle analysis demonstrated that the percentage of cells in G1 phase during serum starvation was reduced from 86.4±2.3 % to 78.3±3.2 % by the inclusion of albumin whereas the percentage of cells in S phase was increased from 6.5±1.5 % to 14.3±3.6 %. A significant reduction in the cell cycle inhibitor protein, P21, accompanied the changes in the proportions of cell cycle phases upon treatment with albumin. We have also observed that the levels of dead cells determined by DNA fragmentation and membrane permeabilization caused by serum starvation (TUNEL: 16.6 ± 7.2 %, ethidium bromide: 13.8±4.8 %) were not significantly altered by the inclusion of albumin (11.6 ± 10.2 %, ethidium bromide: 16.9 ± 8.9 %). Therefore, the increase in cell number was mainly caused by albumin promoting proliferation rather than protection against cell death. These primary findings demonstrate that albumin has immediate effects on HepG2/C3A hepatocellular carcinoma cells. These effects should be taken into consideration when studying the effects of albumin bound drugs or pathological ligands bound to albumin on HepG2/C3A cells.

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Impaired cell functions of hepatocytes incubated with plasma of septic patients

Abstract: The plasma of patients with septic shock impaired cellular functions of HepG2/C3A cells.

Cited by 15 publications

References 44 publications

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

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

Albumin promotes proliferation of G1 arrested serum starved hepatocellular carcinoma cells

Peer Review #2 of "Albumin promotes proliferation of G1 arrested serum starved hepatocellular carcinoma cells (v0.1)"

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