A novel approach to adenine-induced chronic kidney disease associated anemia in rodents
Rahman A. Yamazaki D. Sufiun A. Kitada K. Hitomi H. Nakano D. Nishiyama A.
Rahman A.
Yamazaki D.
Sufiun A.
Hitomi H.
Nakano D.
Nishiyama A.
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Alternative Title
Abstract
To date, good experimental animal models of renal anemia are not available. Therefore, the purpose of this study was to establish a novel approach to induce chronic kidney disease (CKD) with severe anemia by oral administration of adenine in rodents. Adenine was administered to 6-week-old male C57BL/6 mice (25 and 50 mg/kg body weight) by oral gavage daily for 28 days. Serum creatinine and BUN as well as hematocrit, hemoglobin (Hb) and plasma erythropoietin (EPO) levels were monitored to assess renal function and anemia, respectively. Adenine at 25 mg/kg for 28 days slightly increased plasma creatinine levels, but did not induce anemia. In contrast, 50 mg/kg of adenine daily for 28 days showed severe renal dysfunction (plasma creatinine 1.9 ± 0.10 mg/dL) and anemia (hematocrit 36.5 ± 1.0% and EPO 28 ± 2.4 pg/mL) as compared with vehicle-treated mice (0.4 ± 0.02 mg/dL, 49.6 ± 1.6% and 61 ± 4.0 pg/mL, respectively). At the end of experiment, level of Hb also significantly reduced in 50 mg/kg adenine administration group. Remarkable histological changes of kidney tissues characterized by interstitial fibrosis and cystic appearance in tubules were observed in 50 mg/kg of adenine treatment group. These results have demonstrated that oral dosing with adenine at 50 mg/kg for 28 days is suitable to induce a stable anemia associated with CKD in mice. © 2018 Rahman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords
adenine, alpha smooth muscle actin, creatinine, erythropoietin, fibroblast growth factor 23, hemoglobin, recombinant erythropoietin, adenine, creatinine, erythropoietin, hemoglobin, anemia, animal experiment, animal model, animal tissue, Article, chronic kidney failure, controlled study, creatinine blood level, disease association, disease severity, female, ferritin blood level, Fgf23 gene, gamma glutamyl transferase blood level, gene expression, hematocrit, hemoglobin blood level, kidney fibrosis, kidney injury, kidney structure, male, mouse, nonhuman, protein blood level, rat, Sma gene, urea nitrogen blood level, anemia, animal, blood, C57BL mouse, chemically induced, chronic kidney failure, complication, dose response, drug effects, kidney, metabolism, pathology, pathophysiology, Wistar rat, Adenine, Anemia, Animals, Blood Urea Nitrogen, Creatinine, Dose-Response Relationship, Drug, Erythropoietin, Hematocrit, Hemoglobins, Kidney, Kidney Failure, Chronic, Male, Mice, Mice, Inbred C57BL, Rats, Rats, Wistar
Source Title
PLoS ONE
Publisher
Public Library of Science
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Date
2018
DOI
10.1371/journal.pone.0192531
Type
Article