Doxorubicin‐induced platelet cytotoxicity: a new contributory factor for doxorubicin‐mediated thrombocytopenia

Kim, Eun‐Jung; Lim, Kyung Min; Kim, Kyoung-Yun; Bae, Ok Nam; Noh, Jin-Yong; Chung, Seung Min; Shin, Sue; Yun, Young Won; Chung, Jin Ho

doi:10.1111/j.1538-7836.2009.03477.x

Cited by 59 publications

(46 citation statements)

References 38 publications

(47 reference statements)

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“…It enables real-time detection of treatment-induced complications in the same animal over an extended period of time. We evaluated two classes of chemotherapies: doxorubicin which is known to be toxic to endothelial cells in vitro as well as in tissues obtained from animals treated with doxorubicin [10][11][12][13][14][15] , and paclitaxel as a control chemotherapy for which the former evidence for any vascular effect is very limited.…”

Section: Discussionmentioning

confidence: 99%

Chemotherapy-induced Vascular Toxicity - Real-time <em>In vivo</em> Imaging of Vessel Impairment

Bar‐Joseph

Stemmer

Tsarfaty

et al. 2015

JoVE

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Certain classes of chemotherapies may exert acute vascular changes that may progress into long-term conditions that may predispose the patient to an increased risk of vascular morbidity. Yet, albeit the mounting clinical evidence, there is a paucity of clear studies of vascular toxicity and therefore the etiology of a heterogeneous group of vascular/cardiovascular disorders remains to be elucidated. Moreover, the mechanism that may underlie vascular toxicity can completely differ from the principles of chemotherapy-induced cardiotoxicity, which is related to direct myocyte injury. We have established a real-time, in vivo molecular imaging platform to evaluate the potential acute vascular toxicity of anti-cancer therapies.We have set up a platform of in vivo, high-resolution molecular imaging in mice, suitable for visualizing vasculature within confined organs and reference blood vessels within the same individuals whereas each individual serve as its own control. Blood vessel walls were impaired after doxorubicin administration, representing a unique mechanism of vascular toxicity that may be the early event in end-organ injury. Herein, the method of fibered confocal fluorescent microscopy (FCFM) based imaging is described, which provides an innovative mode to understand physiological phenomena at the cellular and sub-cellular levels in animal subjects. Video LinkThe video component of this article can be found at

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Section: Discussionmentioning

confidence: 99%

Chemotherapy-induced Vascular Toxicity - Real-time <em>In vivo</em> Imaging of Vessel Impairment

Bar‐Joseph

Stemmer

Tsarfaty

et al. 2015

JoVE

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“…LdH has an important role in the energy metabolism of platelets, so its inhibition or leakage as in the case of doxorubicin can be cytotoxic to platelets [14]. Ketoprofen has its efficacy established as an anti-inflammatory and analgesic agent [15,16].…”

Section: Discussionmentioning

confidence: 99%

Effect of Ketoprofen on Lactic Dehydrogenase from Human Platelets

et al. 2014

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Background. In different clinical investigations of thrombocytopenia, ketoprofen was found to be the associated cause. Ketoprofen alone or in combination with other therapeutic regimens leads to a decrease in platelet count. Thrombocytopenia due to ketoprofen use can be a threatening condition to the patients who require uncompromised platelet function. Objectives. In order to establish a mechanism for thrombocytopenia associated with ketoprofen use, the enzyme inhibition effects of ketoprofen on lactic dehydrogenase (LdH) were investigated in this study. LdH is essentially involved in platelet energy production. Material and Methods. LdH isolated from human platelets was subjected to different concentrations of ketoprofen (250, 500, 750, 1000 and 1500 µg/mL) and pyruvate as a substrate (45, 60 and 90 µM/mL) to gain insight into the enzyme inhibition effects for forward reaction. Oxidation of nicotinamide adenine dinucleotide (NadH) was measured at 340 nm to evaluate enzyme activity. enzyme inhibition kinetics were studied via Lineweaver burk plot. Results. Ketoprofen was found to be a competitive inhibitor of LdH in human platelets. 89% of enzyme activity was inhibited by a 1500 µg/mL concentration of the drug and the enzyme inhibition constant was 882 µg/mL. Conclusions. The possible main cause of thrombocytopenia due to ketoprofen use is LdH inhibition in platelets, which are essential for platelet energy metabolism. So patients who require uncompromised platelet function and are receiving ketoprofen in their prescription should be monitored for platelet count and blood clotting (Adv Clin Exp Med 2014, 23, 3, 377-380).

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“…14 Observations of Kim et al 15 have found that doxorubicin can induce procoagulant activity; and what is more, ROS production is involved in this process. Moreover, results of Kim et al 15 showed that doxorubicin can induce cytotoxicity in blood platelets through ROS generation and also decrease glutathione or protein thiol levels. Increased complication of thrombotic disorders is well documented in cancer patients treated with other ROS-generating chemotherapeutic drugs (bleomycin or cisplatin).…”

Section: Oxidative Stress In Breast Cancermentioning

confidence: 96%

“…[7][8][9][10][11][12][13] ROS produced during cancer chemotherapy are often a source of serious side effects (cardiotoxicity, nephrotoxicity, ototoxicity, and hematological toxicity). 14,15 The oxidative stress, detected by using various biomarkers (including the level of carbonyl groups and 3-nitrotyrosine in proteins, the total antioxidant level (TAS), the activity of antioxidative enzymes), had been observed in breast cancer patients before and during different phases of treatment. [7][8][9][10][11][12][13][16][17][18][19][20][21][22][23] Results of Kedzierska et al 11 have shown that the total level of glutathione (an important physiological antioxidant) in plasma isolated from breast cancer patients (before and during treatment, during different phases of chemotherapy (doxorubicin and cyclophosphamide)) was lower than in healthy persons.…”

Section: Oxidative Stress In Breast Cancermentioning

confidence: 99%

Role of Black Chokeberries in Breast Cancer

Olas

2014

Cancer

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Doxorubicin‐induced platelet cytotoxicity: a new contributory factor for doxorubicin‐mediated thrombocytopenia

Cited by 59 publications

References 38 publications

Chemotherapy-induced Vascular Toxicity - Real-time <em>In vivo</em> Imaging of Vessel Impairment

Chemotherapy-induced Vascular Toxicity - Real-time <em>In vivo</em> Imaging of Vessel Impairment

Effect of Ketoprofen on Lactic Dehydrogenase from Human Platelets

Role of Black Chokeberries in Breast Cancer

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