Evaluation of the hepatocyte-derived cell line BFH12 as an in vitro model for bovine biotransformation

Gleich, Alexander; Kaiser, Bastian; Honscha, Walther; Fuhrmann, Herbert; Schoeniger, Axel

doi:10.1007/s10616-018-0279-4

Cited by 11 publications

(9 citation statements)

References 64 publications

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“…In established hepatic cell lines, the basal gene expression profiles, and the corresponding phenotype, may differ substantially from hepatocyte primary cultures, the gold standard for studying xenobiotics metabolism and toxicity [59]. As for the BFH12 cell line, a partial characterization of constitutive and inducible mRNA levels of foremost drug metabolizing enzymes and transporters has already been made [45,46]; however, no whole-transcriptomic data have been published so far. Assuming the metabolic competence of fetal hepatocytes is lower compared to that of adult liver cells, we opted for pre-treatment with an AHR agonist, i.e., PCB126, to increase the cell line metabolic competence, hence the responsiveness to AFB1.…”

Section: Preliminary Evaluations Of Bfh12 Responsiveness To Pcb126mentioning

confidence: 99%

“…Based on these considerations, the aim of the present study was to assess in vitro the overall transcriptional changes (RNA-seq) caused by AFB1 in a bovine fetal hepatocyte-derived cell line (BFH12). This cell line constitutively expresses most cattle drug metabolizing enzymes and transporters [45,46], but its transcriptome has not been fully characterized so far. With the intent to have a greater response of the aforementioned in vitro model, cells were pre-treated with the co-planar polychlorinated biphenyl 3,3 ,4,4 ,5-pentachlorobiphenyl (PCB126), a known agonist of the aryl hydrocarbon receptor (AHR) [47].…”

Section: Introductionmentioning

confidence: 99%

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Insights into Aflatoxin B1 Toxicity in Cattle: An In Vitro Whole-Transcriptomic Approach

Pauletto

Tolosi²,

Giantin³

et al. 2020

Toxins

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Aflatoxins, and particularly aflatoxin B1 (AFB1), are toxic mycotoxins to humans and farm animal species, resulting in acute and chronic toxicities. At present, AFB1 is still considered a global concern with negative impacts on health, the economy, and social life. In farm animals, exposure to AFB1-contaminated feed may cause several untoward effects, liver damage being one of the most devastating ones. In the present study, we assessed in vitro the transcriptional changes caused by AFB1 in a bovine fetal hepatocyte-derived cell line (BFH12). To boost the cellular response to AFB1, cells were pre-treated with the co-planar PCB 3,3′,4,4′,5-pentachlorobiphenyl (PCB126), a known aryl hydrocarbon receptor agonist. Three experimental groups were considered: cells exposed to the vehicle only, to PCB126, and to PCB126 and AFB1. A total of nine RNA-seq libraries (three replicates/group) were constructed and sequenced. The differential expression analysis showed that PCB126 induced only small transcriptional changes. On the contrary, AFB1 deeply affected the cell transcriptome, the majority of significant genes being associated with cancer, cellular damage and apoptosis, inflammation, bioactivation, and detoxification pathways. Investigating mRNA perturbations induced by AFB1 in cattle BFH12 cells will help us to better understand AFB1 toxicodynamics in this susceptible and economically important food-producing species.

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Section: Preliminary Evaluations Of Bfh12 Responsiveness To Pcb126mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Insights into Aflatoxin B1 Toxicity in Cattle: An In Vitro Whole-Transcriptomic Approach

Pauletto

Tolosi²,

Giantin³

et al. 2020

Toxins

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“…Therefore, it has protective capacity to interrupt the absorption, permeability, and retention of the drugs. [ 45 ] Ligand along with hydroxychloroquine shows type III acute oral toxicity. Ligand HNP‐Hn‐HNPH 2 indicates good inhibitor for human ether‐a‐go‐go‐related gene (hERG) that can lead to short QT syndrome.…”

Section: Resultsmentioning

confidence: 99%

Titanium (IV) complexes of some tetra‐dentate symmetrical bis‐Schiff bases of 1,6‐hexanediamine: Synthesis, characterization, and in silico prediction of potential inhibitor against coronavirus (SARS‐CoV‐2)

Uddin

Amin

Rahman

et al. 2020

Applied Organom Chemis

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Symmetrical bis-Schiff bases (LH 2) have been synthesized by the condensation of 1,6-hexanediamine (hn) and carbonyl or dicarbonyl. One of the synthesized Schiff bases has been subjected to the molecular docking for the prediction of their potentiality against coronavirus (SARS-CoV-2). Molecular docking revealed that tested Schiff base possessed high binding affinity with the receptor protein of SARS CoV-2 compared with hydroxychloroquine (HCQ). The ADMET analysis showed that ligand is non-carcinogenic and less toxic than standard HCQ. Schiff bases acting as dibasic tetra-dentate ligands formed titanium (IV) complexes of the type [TiL(H 2 O) 2 Cl 2 ] or [TiL(H 2 O) 2 ]Cl 2 being coordinated through ONNO donor atoms. Ligands and complexes were characterized by the elemental analysis and physicochemical and spectroscopic data including FTIR, 1 H NMR, mass spectra, UV-Visible spectra, molar conductance, and magnetic measurement. Optimized structures obtained from quantum chemical calculations supported the formation of complexes. Antibacterial, antifungal, and anti-oxidant activity assessments have been studied for synthesized ligands and complexes.

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“…Immortalized bovine fetal hepatocytes (BFH-12, Cellosaurus accession CVCL_JQ51) were purchased from Dr. Herber Fuhrmann (University of Leipzig, Leipzig, Germany) and were grown in vented T75 flasks (cat# 25-209, Olympus Plastics, Genesee Scientific, San Diego, CA, USA) in Williams' E Medium (cat# A1217601, Gibco, Thermo Fisher Scientific, Waltham, MA, USA) containing 5% FBS, 1% penicillin/streptomycin, 1% GlutaMAX supplement (cat# 35050061, Gibco), 100 nM of dexamethasone (cat# AAA17590, Alfa Aesar, Haverhill, MA, USA), and 0.2 U/mL of insulin (cat# I6634, Sigma-Aldrich), at 37 • C, with 5% CO 2 . Culture media choices and environmental conditions reflect the protocols developed in the original publication [18]. Cells were cultured for at least 3 passages before the beginning of each experiment.…”

Section: Cell Culture and Treatmentsmentioning

confidence: 99%

“…Utilizing albumin-bound FA would be more representative of a physiological state; however, it is unclear whether physiological mechanisms for the uptake of albumin-bound FA (discussed in [6]) would be maintained in a cell culture model. Ultimately, our approach provides the greatest degree of response, and as such allows to determine individual differences with greater precision; (4) BFH-12 are hepatocytes isolated and established from bovine fetuses [18] and are likely not fully representative of adult bovine hepatocytes, since the liver of calves is still maturing after few weeks post-birth [45]. However, the model should be reliable in determining the relative difference in activation and the additive effects of various FA on PPAR activation.…”

Section: Limitations Of the Studymentioning

confidence: 99%

When Two plus Two Is More than Four: Evidence for a Synergistic Effect of Fatty Acids on Peroxisome Proliferator—Activated Receptor Activity in a Bovine Hepatic Model

Busato

Bionaz

2021

Genes

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The inclusion of fat in livestock diets represents a valuable and cost-effective way to increase the animal’s caloric intake. Beyond their caloric value, fatty acids can be understood in terms of their bioactivity, via the modulation of the ligand-dependent nuclear peroxisome proliferator-activated receptors (PPAR). Isotypes of PPAR regulate important metabolic processes in both monogastric and ruminant animals, including the metabolism of fatty acids (FA), the production of milk fat, and the immune response; however, information on the modulation of bovine PPAR by fatty acids is limited. The objective of this study was to expand our understanding on modulation of bovine PPAR by FA, both when used individually and in combination, in an immortalized cell culture model of bovine liver. Of the 10 FA included in the study, the greatest activation of the PPAR reporter was detected with saturated FA C12:0, C16:0, and C18:0, as well as phytanic acid, and the unsaturated FA C16:1 and C18:1. When supplemented in mixtures of 2 FA, the most effective combination was C12:0 + C16:0, while in mixtures of 3 FA, the greatest activation was caused by combinations of C12:0 with C16:0 and either C18:0, C16:1, or C18:1. Some mixtures display a synergistic effect that leads to PPAR activation greater than the sum of their parts, which may be explained by structural dynamics within the PPAR ligand-binding pocket. Our results provide fundamental information for the development of tailored dietary plans that focus on the use of FA mixtures for nutrigenomic purposes.

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Evaluation of the hepatocyte-derived cell line BFH12 as an in vitro model for bovine biotransformation

Cited by 11 publications

References 64 publications

Insights into Aflatoxin B1 Toxicity in Cattle: An In Vitro Whole-Transcriptomic Approach

Insights into Aflatoxin B1 Toxicity in Cattle: An In Vitro Whole-Transcriptomic Approach

Titanium (IV) complexes of some tetra‐dentate symmetrical bis‐Schiff bases of 1,6‐hexanediamine: Synthesis, characterization, and in silico prediction of potential inhibitor against coronavirus (SARS‐CoV‐2)

When Two plus Two Is More than Four: Evidence for a Synergistic Effect of Fatty Acids on Peroxisome Proliferator—Activated Receptor Activity in a Bovine Hepatic Model

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