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

Animals ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 30
Author(s):  
Lidia Radko ◽  
Tomasz Śniegocki ◽  
Bartosz Sell ◽  
Andrzej Posyniak

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.

1990 ◽  
Vol 17 (3) ◽  
pp. 240-245
Author(s):  
Ramiro Jover ◽  
Xavier Ponsoda ◽  
Jose Vicente Castell ◽  
Maria José Gómez-Lechón

We have studied the hepatotoxic effects of cocaine and opioids (morphine, heroin, meperidine, methadone and buprenorphine) on two experimental cellular systems: primary monolayer cultures of rat hepatocytes and hepatoma cell lines (FaO and Hep G2). Three methods were used to evaluate cytotoxicity: intracellular measurement of LDH activity, measurement of total attached cellular protein content, and the MTT test. The results show that: 1) Morphine, heroin and cocaine were more toxic to 1-24-hour primary cultures (IC50: 0.16-0.56mM) than to the other liver-derived cells (IC50: 0.62-8.00mM). 2) Meperidine and methadone produced more evident toxic effects on the hepatoma cell lines (IC50: 0.6–2.0 and 0.08–0.25mM, respectively) than on the primary hepatocyte cultures (IC50: 1.7–4.5 and 0.25–0.50mM, respectively). 3) The toxicity of buprenorphine was similar in all cellular systems (IC50: 0.03–0.13mM). 4) With regard to their toxic potential, we found that buprenorphine and methadone were the most toxic compounds in the majority of the tests. On the other hand, meperidine was least toxic to primary hepatocyte cultures, but showed higher toxicity than morphine, heroin and cocaine to the hepatoma cell lines.


1998 ◽  
Vol 55 (7) ◽  
pp. 1059-1069 ◽  
Author(s):  
Christopher Hassett ◽  
Elizabeth M Laurenzana ◽  
Jaspreet S Sidhu ◽  
Curtis J Omiecinski

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