Metabolomic Profile of Primary Turkey and Rat Hepatocytes and Two Cell Lines after Chloramphenicol Exposure.

Animals (Basel)

Department of Pharmacology and Toxicology, National Veterinary Research Institute, Al. Partyzantów 57, 24-100 Puławy, Poland.

Published: December 2019

The purpose of this study was to assess the formation of chloramphenicol metabolites in primary turkey and rat hepatocyte cultures and human hepatoma (HepG2) cells and nonhepatic, Balb/c 3T3 fibroblasts. Additionally, the cytotoxicity of the drug was assessed through three biochemical endpoints: mitochondrial and lysosomal activity and cellular membrane integrity after 24 and 48 h exposure. The two metabolites of the drug, chloramphenicol glucuronide and nitroso-chloramphenicol, were detected to the greatest extent in both primary hepatocyte cultures by liquid chromatography-tandem mass spectrometry. Toxic nitroso-chloramphenicol was the main metabolite in the primary turkey hepatocyte cultures, but it was not in the primary rat hepatocyte cultures. The most affected endpoint in turkey and rat hepatocyte cultures was the disintegration of the cellular membrane, but in the cell lines, mitochondrial and lysosomal activities underwent the greatest change. The primary hepatocyte cultures represent valuable tools with which to study the species differences in the biotransformation and toxicity of drugs. To the best of our knowledge, this is the first report of differences in chloramphenicol metabolism in primary turkey and rat hepatocyte cultures.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022860PMC
http://dx.doi.org/10.3390/ani10010030DOI Listing

Publication Analysis

Top Keywords

hepatocyte cultures
28
primary turkey
16
turkey rat
16
rat hepatocyte
16
cell lines
8
mitochondrial lysosomal
8
cellular membrane
8
primary hepatocyte
8
primary
7
hepatocyte
7

Similar Publications

A new human autologous hepatocyte/macrophage co-culture system that mimics drug-induced liver injury-like inflammation.

Arch Toxicol

December 2024

Department of Hepatobiliary Surgery and Visceral Transplantation, Clinic and Polyclinic for Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig University Medical Center, Leipzig, Germany.

The development of in vitro hepatocyte cell culture systems is crucial for investigating drug-induced liver injury (DILI). One prerequisite for monitoring DILI related immunologic reactions is the extension of primary human hepatocyte (PHH) cultures towards the inclusion of macrophages. Therefore, we developed and characterized an autologous co-culture system of PHH and primary human hepatic macrophages (hepM) (CoC1).

View Article and Find Full Text PDF

Background: Recent studies suggest a contribution of intrahepatic mineralocorticoid receptor (MR) activation to the development of cirrhosis. As MR blockade abrogates the development of cirrhosis and hypoxia, common during the development of cirrhosis, can activate MR in hepatocytes. But, the impact of non-physiological hepatic MR activation is unknown.

View Article and Find Full Text PDF

Triglyceride (TG) and its derivatives tend to be decreased in rheumatoid arthritis (RA) patients' blood when inflammation progresses. Aside from the role as a lipid buffer, white adipose tissue (WAT) contributes to this abnormality via adipokines, which regulate many metabolic signals. This work investigated adipokine-caused hepatic changes and their involvement in RA-related hypolipemia.

View Article and Find Full Text PDF

Background: Routine liver function tests capture information about the metabolic and inflammatory condition of the liver, but we lack sensitive biomarkers of early hepatocyte stress. In humans, soluble CD46 (sCD46) levels in blood were recently identified as an accurate biomarker of hepatic steatosis. Here, we explore the diagnostic utility of sCD46 in other liver diseases.

View Article and Find Full Text PDF

The de-ubiquitinase USP33 has been shown to possess either tumour-promoting or inhibitory effect on human cancer cells. However, all these findings are mainly based on in vitro cell culture models, and the in vivo evidence, which is more plausible to digest the functional role of USP33 in carcinogenic process, is still lacking. Here, we demonstrate that USP33 modulates DNA damage responses including cell cycle arrest and apoptosis induction through associating with p53.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!