Mechanism underlying linezolid-induced thrombocytopenia in a chronic kidney failure mouse model

Nao Nishijo, Yasuhiro Tsuji, Kazuhisa Matsunaga, Masahiko Kutsukake, Fumiyasu Okazaki, Shiro Fukumori, Hidefumi Kasai, Yoichi Hiraki, Ippei Sakamaki, Yoshihiro Yamamoto, Yoshiharu Karube, Hideto To

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Abstract

Objective: To investigate the relationship between renal function and linezolid (LZD)-induced thrombocytopenia and elucidate the underlying mechanism using a chronic renal disease (CRD) mouse model. Materials and Methods: CRD was induced in 5-week-old male Institute of Cancer Research (ICR) mice by 5/6 nephrectomy. After this procedure, LZD (25 and 100 mg/kg) was administered intraperitoneally once every day for 28 days. Platelet counts, white blood cell (WBC) counts, and hematocrit (HCT) levels were measured every 7 days. 2-14C-thymidine (0.185 MBq) was administrated intravenously to LZD-administered mice to evaluate the thymidine uptake ability of bone marrow. Results: Platelet counts were significantly lower in the LZD-administered CRD group than in the LZD-nonadministered groups at 14, 21, and 28 days (P < 0.05); however, these changes were not observed in LZD-administered mice with normal renal function, regardless of the duration of LZD administration. No significant changes were observed in WBC counts or HCT levels in any LZD-administered CRD mouse. Moreover, radioactive levels in bone marrow were not significantly different in each group. Conclusions: These results indicate that LZD-induced decreases in platelet counts were enhanced by renal impairment in vivo, suggesting that LZD-induced thrombocytopenia is not caused by nonimmune-mediated bone marrow suppression.

Original languageEnglish
Pages (from-to)8-13
Number of pages6
JournalJournal of Pharmacology and Pharmacotherapeutics
Volume8
Issue number1
DOIs
Publication statusPublished - 2017 Jan 1
Externally publishedYes

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Keywords

  • Chronic renal disease model mouse
  • DNA synthesis ability
  • hematological effect
  • linezolid
  • thrombocytopenia

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Nishijo, N., Tsuji, Y., Matsunaga, K., Kutsukake, M., Okazaki, F., Fukumori, S., Kasai, H., Hiraki, Y., Sakamaki, I., Yamamoto, Y., Karube, Y., & To, H. (2017). Mechanism underlying linezolid-induced thrombocytopenia in a chronic kidney failure mouse model. Journal of Pharmacology and Pharmacotherapeutics, 8(1), 8-13. https://doi.org/10.4103/jpp.JPP_167_16