jrnls.org logo
Submit

BROWSE ALL JOURNALS

SEE ALL 19 JOURNALS
Journal of Pharmacology and PharmacotherapeuticsNOW IN
Article

Mechanism Underlying Linezolid‑induced Thrombocytopenia in a Chronic Kidney Failure Mouse Model

Nao Nishijo2, Yasuhiro Tsuji2★, Kazuhisa Matsunaga3, Masahiko Kutsukake2, Fumiyasu Okazaki2, Shiro Fukumori2, Hidefumi Kasai2,4, Yoichi Hiraki5, Ippei Sakamaki6, Yoshihiro Yamamoto6, Yoshiharu Karube3, Hideto To2★ Corresponding author

  1. 1Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, Japan.
  2. 2Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814‑0180, Japan.
  3. 3Certara G.K., Minato‑Ku, Tokyo 105‑0001, Japan.
  4. 4Department of Pharmacy, National Hospital Organization Beppu Medical Center, Beppu, Oita, 874‑0011, Japan.
  5. 5Department of Clinical Infectious Diseases, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama 930‑0194, Japan.

CORRESPONDENCE

Yasuhiro Tsuji

Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814‑0180, Japan.

ytsuji@pha.u‑toyama.ac.jp

Received: 27-10-2016; Revised: 29-12-2016; Accepted: 27-01-2017.

Volume 8, Issue 1 · pp. 8–13 · PUBLISHED 2017 · DOI: 10.4103/jpp.JPP_167_16

View on JPP original site ↗

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.

KEYWORDS

Open in new tab

REFERENCES

As published

Showing references and in-text citations exactly as published.

    Cite this article

    SELECT FORMAT

    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