Wang Tianlin, Guo Daihong, Dong Xianzhe, Mu Lihua
Department of Pharmaceutical Care, General Hospital of People's Liberation Army, Beijing, China.
J Antibiot (Tokyo). 2014 Jun;67(6):433-7. doi: 10.1038/ja.2014.21. Epub 2014 Apr 2.
Effect of linezolid is associated with hematocytopenia. A possible relationship between oxidative stress and hematologic toxicity has also been discussed. This present study was performed to determine the effect of oral administration of linezolid on hematological and oxidative parameters in rats. Rats were divided into five groups of 20 each. Drugs were given for a 15-day period. Control rats were vehicle treated. In the second and third groups, linezolid (50 and 125 mg kg(-1)) was given to rats twice a day (100 and 250 mg kg(-1) per day) orally by gavage. The fourth group was given diet supplement that contained 250 mg kg(-1) Vitamin E. The fifth group was given 125 mg kg(-1) linezolid twice a day along with Vitamin E supplement. Blood cell counts (red blood cell (RBC), white blood cell (WBC) and platelet) were measured every 5 days. Enzymatic antioxidant activities, lipid peroxidation and free radical production were performed at the end of 15th day. The results showed that linezolid induces a decrease of WBC, RBC and platelet numbers in rat blood and enzymatic activities of superoxide dismutase and catalase in rat serum in a dose-dependent manner. While the content of malondialdehyde and nitric oxide was significantly increased in rats serum compared with the control group, Vitamin E supplement could partially reverse the above changes without affecting the control group. The results suggest that linezolid has effect on decreasing hemocyte level in rats, and oxidative stress may be one of the major causative factors. Antioxidant may prove to be a useful therapeutic option in the reversal of hematologic effects induced by linezolid.
利奈唑胺的作用与血细胞减少有关。氧化应激与血液毒性之间的可能关系也已被讨论。本研究旨在确定口服利奈唑胺对大鼠血液学和氧化参数的影响。大鼠被分为五组,每组20只。给药15天。对照组大鼠接受赋形剂处理。在第二组和第三组中,给大鼠每日两次口服利奈唑胺(50和125mg/kg)(每天100和250mg/kg)。第四组给予含有250mg/kg维生素E的饮食补充剂。第五组每日两次给予125mg/kg利奈唑胺并同时给予维生素E补充剂。每5天测量血细胞计数(红细胞(RBC)、白细胞(WBC)和血小板)。在第15天结束时进行酶促抗氧化活性、脂质过氧化和自由基产生的检测。结果表明,利奈唑胺以剂量依赖性方式导致大鼠血液中白细胞、红细胞和血小板数量减少以及大鼠血清中超氧化物歧化酶和过氧化氢酶的酶活性降低。与对照组相比,大鼠血清中丙二醛和一氧化氮的含量显著增加,补充维生素E可部分逆转上述变化,且不影响对照组。结果表明,利奈唑胺对降低大鼠血细胞水平有作用,氧化应激可能是主要致病因素之一。抗氧化剂可能被证明是逆转利奈唑胺所致血液学效应的一种有用的治疗选择。