Dichloroacetate Prevents Cisplatin-Induced Nephrotoxicity without Compromising Cisplatin Anticancer Properties
| العنوان: | Dichloroacetate Prevents Cisplatin-Induced Nephrotoxicity without Compromising Cisplatin Anticancer Properties |
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| المؤلفون: | Kristine Hardy, Luyang Tian, Linda McMorrow, Jane E. Dahlstrom, Melissa Rooke, Hardip R. Patel, Anneke C. Blackburn, Philip G. Board, Elize Wium, Jean Cappello, Aaron Chuah, Angelo Theodoratos, Ramindhu Galgamuwa, Padmaja Tummala |
| المصدر: | Journal of the American Society of Nephrology. 27:3331-3344 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Antineoplastic Agents, Dichloroacetic acid, Oxidative phosphorylation, Pharmacology, Biology, medicine.disease_cause, Nephrotoxicity, Mice, 03 medical and health sciences, chemistry.chemical_compound, Downregulation and upregulation, medicine, Animals, Cisplatin, Mice, Inbred BALB C, Creatinine, Dichloroacetic Acid, General Medicine, Basic Research, 030104 developmental biology, chemistry, Nephrology, Apoptosis, Female, Kidney Diseases, Oxidative stress, medicine.drug |
| الوصف: | Cisplatin is an effective anticancer drug; however, cisplatin use often leads to nephrotoxicity, which limits its clinical effectiveness. In this study, we determined the effect of dichloroacetate, a novel anticancer agent, in a mouse model of cisplatin-induced AKI. Pretreatment with dichloroacetate significantly attenuated the cisplatin-induced increase in BUN and serum creatinine levels, renal tubular apoptosis, and oxidative stress. Additionally, pretreatment with dichloroacetate accelerated tubular regeneration after cisplatin-induced renal damage. Whole transcriptome sequencing revealed that dichloroacetate prevented mitochondrial dysfunction and preserved the energy-generating capacity of the kidneys by preventing the cisplatin-induced downregulation of fatty acid and glucose oxidation, and of genes involved in the Krebs cycle and oxidative phosphorylation. Notably, dichloroacetate did not interfere with the anticancer activity of cisplatin in vivo. These data provide strong evidence that dichloroacetate preserves renal function when used in conjunction with cisplatin. |
| تدمد: | 1533-3450 1046-6673 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a50b0a9d5fd2ca8fd36d31d297fec93a https://doi.org/10.1681/asn.2015070827 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....a50b0a9d5fd2ca8fd36d31d297fec93a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15333450 10466673 |
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