Journal of Pharmacology and Pharmacotherapeutics

RESEARCH PAPER
Year
: 2017  |  Volume : 8  |  Issue : 1  |  Page : 8--13

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


Nao Nishijo1, Yasuhiro Tsuji1, Kazuhisa Matsunaga2, Masahiko Kutsukake1, Fumiyasu Okazaki1, Shiro Fukumori1, Hidefumi Kasai3, Yoichi Hiraki4, Ippei Sakamaki5, Yoshihiro Yamamoto5, Yoshiharu Karube2, Hideto To1 
1 Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan
2 Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan
3 Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194; Certara G.K., Minato-Ku, Tokyo 105-0001, Japan
4 Department of Pharmacy, National Hospital Organization Beppu Medical Center, Beppu, Oita, 874-0011, Japan
5 Department of Clinical Infectious Diseases, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama 930-0194, India

Correspondence Address:
Yasuhiro Tsuji
Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194
Japan

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.


How to cite this article:
Nishijo N, Tsuji Y, Matsunaga K, Kutsukake M, Okazaki F, Fukumori S, Kasai H, Hiraki Y, Sakamaki I, Yamamoto Y, Karube Y, To H. Mechanism underlying linezolid-induced thrombocytopenia in a chronic kidney failure mouse model.J Pharmacol Pharmacother 2017;8:8-13


How to cite this URL:
Nishijo N, Tsuji Y, Matsunaga K, Kutsukake M, Okazaki F, Fukumori S, Kasai H, Hiraki Y, Sakamaki I, Yamamoto Y, Karube Y, To H. Mechanism underlying linezolid-induced thrombocytopenia in a chronic kidney failure mouse model. J Pharmacol Pharmacother [serial online] 2017 [cited 2017 Jul 23 ];8:8-13
Available from: http://www.jpharmacol.com/article.asp?issn=0976-500X;year=2017;volume=8;issue=1;spage=8;epage=13;aulast=Nishijo;type=0