Elucidating the Mechanism of 6-mercaptopurine Induced Hepatotoxicity and How Combination with Allopurinol Eliminates the Hepatotoxicity*
| Autor: | Bethany Cunningham, Jayasree Krishnamurthy, Jennifer Deutsch, Lab Assistant, Michael Flora, Kenneth Lieuw |
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| Rok vydání: | 2018 |
| Předmět: |
Drug
Thiopurine methyltransferase biology business.industry Metabolite Liver cell media_common.quotation_subject Allopurinol Pharmacology medicine.disease Mercaptopurine Inflammatory bowel disease chemistry.chemical_compound chemistry Acute lymphocytic leukemia Pediatrics Perinatology and Child Health biology.protein Medicine business medicine.drug media_common |
| Zdroj: | Section on Uniformed Services Program. |
| Popis: | Objectives: 6-Mercaptopurine (6MP) is an immunosuppressive thiopurine drug used for the treatment of diseases such as inflammatory bowel disease and acute lymphocytic leukemia. 6MP is converted to thioguanine nucleotide (6TGN), which is the desired metabolite responsible for myelosuppression, or to 6-methylmercaptopurine (6MMPN), which is associated with hepatotoxicity (see fig. 1). In patients, the combined use of allopurinol with 6MP was found to decrease 6MMPN levels eliminating hepatotoxicity while maintaining efficacy with higher 6TGN levels. How 6MP results in hepatotoxicity is unclear. Moreover, the mechanism by which allopurinol lowers hepatotoxicity is unknown. Our objectives were to create a liver cell culture system to better understand how 6MP causes hepatotoxicity and gain insight into the molecular mechanism by which allopurinol eliminates the hepatotoxicity of 6MP. Methods: A tetracycline inducible DNA construct containing TPMT cDNA was transfected into the HepG2 cell … |
| Databáze: | OpenAIRE |
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