Thrombocytopenia in Patients Receiving Prolonged Linezolid May be Caused by Oxidative Stress.
OBJECTIVE
Oxidative stress in drug-induced thrombocytopenia (TP) has been discussed. This study was carried out to assess the oxidative stress in patients with normal platelet count (NPC) and TP after linezolid (LZD) treatment and to evaluate if TP caused by LZD is associated with a reduction in antioxidation ability and an increase in lipid peroxidative product in platelets.


METHODS
After LZD treatment for 20 days, 44 patients with TP and 73 patients with NPC were included in this study. Blood samples were collected on the day before medicine treatment and day 7, 14, and 20 after LZD therapy. Levels of reactive oxygen species (ROS), malondialdehyde (MDA), and cholesterol as well as the activities of antioxidative enzyme were estimated. In addition, we identified 37 patients with TP caused by low-dose methotrexate (7.5-25 mg/week) therapy as a positive control group.


RESULTS
In total, 37.60% of cases presented with TP on the 20th day of LZD administration. Individuals with TP had significantly elevated levels of ROS and MDA, low levels of superoxide dismutase (SOD) and catalase (CAT), significantly decreased high-density lipoprotein-cholesterol, low-density lipoprotein (LDL)-cholesterol levels, and increased oxidized-LDL levels in comparison to individuals with NPC. However, no significant changes in the levels of glutathione-peroxidase were found in the course of time. In all cases with LZD, significant increases in levels of ROS, MDA, and ox-LDL were found in the 20-day samples compared with their respective samples before LZD treatment. Correlation analysis revealed a positive association between platelet count and levels of SOD on day 20 and CAT on days 14 and 20 in plasma, a negative association between platelet count and level of MDA and ROS on days 14 and 20 in patients with LZD-induced TP.


CONCLUSIONS
The oxidative stress markers were increased in LZD-induced TP, suggesting that oxidative damage might be the underlying mechanism.
Department of Pharmaceutical Care, General Hospital of People's Liberation Army, Beijing, China.
Tian-Lin
TL
Wang
Department of Pharmaceutical Care, General Hospital of People's Liberation Army, Beijing, China.
Dai-Hong
DH
Guo
Department of Pharmaceutical Care, General Hospital of People's Liberation Army, Beijing, China.
Yan
Y
Bai
Center of Medicine Clinical Research, General Hospital of People's Liberation Army, 28 Fu-xing Road, Beijing, China.
Ke
K
Wen
Department of Pharmacology, The University of Tennessee Health Science Center, Memphis, TN, USA.
Wen-Yan
WY
Han
Center of Medicine Clinical Research, General Hospital of People's Liberation Army, 28 Fu-xing Road, Beijing, China. wangr_301@163.com.
Rui
R
Wang
D000368:Aged; D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D000069349:Linezolid / Q000009:adverse effects*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D010976:Platelet Count; D011446:Prospective Studies; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase; D013921:Thrombocytopenia / Q000139:chemically induced*
D000975:Antioxidants; D008076:Cholesterol, HDL; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D008315:Malondialdehyde; D002784:Cholesterol; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000069349:Linezolid