Tetracycline-Induced Steatosis in Primary Canine Hepatocyte Cultures

التفاصيل البيبلوغرافية
العنوان: Tetracycline-Induced Steatosis in Primary Canine Hepatocyte Cultures
المؤلفون: Barabara-Anne Martin, David E. Amacher
المصدر: Toxicological Sciences. 40:256-263
بيانات النشر: Oxford University Press (OUP), 1997.
سنة النشر: 1997
مصطلحات موضوعية: Male, medicine.medical_specialty, Tetracycline, Palmitic Acid, Mitochondria, Liver, Biology, Toxicology, chemistry.chemical_compound, Mice, Dogs, Internal medicine, Oxazines, medicine, Animals, Carnitine, Carbon Radioisotopes, Coloring Agents, Cells, Cultured, Triglycerides, Antibacterial agent, Fluorescent Dyes, Triglyceride, Dose-Response Relationship, Drug, Histocytochemistry, Nile red, Palmitoylcarnitine, Lipid metabolism, medicine.disease, Lipid Metabolism, Anti-Bacterial Agents, Rats, Fatty Liver, Endocrinology, medicine.anatomical_structure, chemistry, Liver, Hepatocyte, Disease Susceptibility, Steatosis, Azo Compounds, medicine.drug
الوصف: Primary hepatocyte cultures prepared from male beagle dog liver were used to determine susceptibility of the canine liver to tetracycline-induced steatosis. The effects of the drug on mitochondrial lipid metabolism and intracellular triglyceride accumulation were monitored at the same time that steatosis was detected by light microscopy and quantitated using lipid-specific stains. Exposure of primary canine hepatocyte cultures to tetracycline for 24–48 h resulted in concentration-dependent, significant increases in the Oil Red O-stained lipid inclusions. Microscopic examination of the total stained areas suggested that increases over control levels were due primarily to the increase in the size of the lipid inclusions rather than in the number. Biochemical analyses for triglyceride content and histological staining with Nile red, another neutral lipid-specific dye, confirmed a specific increase in intracellular triglyceride following a 24-h exposure to noncytotoxic levels of tetracycline. β-oxidation studies based on the oxidation of [ 14 C]palmitic acid or [ 14 C]palmitoyl carnitine demonstrated a concentration-dependent inhibition of mitochondrial but not peroxisomal β-oxidation in hepatocytes after a 24-h exposure to tetracycline. In vitro incubation of tetracycline with mitochondria isolated from dog liver showed similar, concentration-dependent inhibition. This study clearly indicates that the canine hepatocyte is susceptible to tetracycline-induced steatosis. Triglyceride accumulation was concomitant with the inhibition of mitochondrial lipid metabolism, indicating that this is a primary mechanism leading to steatosis in dog hepatocytes following tetracycline exposure.
تدمد: 1096-0929
1096-6080
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::535ea915a228467bd808200ba97c4264Test
https://doi.org/10.1093/toxsci/40.2.256Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....535ea915a228467bd808200ba97c4264
قاعدة البيانات: OpenAIRE