Doxorubicin contributes to thrombus formation and vascular injury by interfering with platelet function

Lv, Haichen; Tan, Ruopeng; Liao, Jiawei; Hao, Zhujing; Yang, Xiaolei; Liu, Yang

doi:10.1152/ajpheart.00456.2019

Cited by 17 publications

(15 citation statements)

References 49 publications

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“…These altered biochemical alterations were supported by histological lesions characterized by myocyte congestion and coronary intravascular microthrombi formation. DOX has been previously reported to profoundly reduce vascular blood flow, disintegrate vascular endothelium, and promote GPIIb/IIIa-mediated platelet adhesion and aggregation, all resulting in microthrombi formation [ 56 – 58 ]. The fact that IGESE prevented microthrombi formation in DOX-treated coronary vasculature as evidenced by histopathological results of this study highlighted the possible inherent antithrombotic potential of IGESE ; although, further studies are still needed in this respect in order to validate this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Irvingia gabonensis Seed Extract: An Effective Attenuator of Doxorubicin-Mediated Cardiotoxicity in Wistar Rats

Olorundare

Adeneye

Akinsola

et al. 2020

Oxidative Medicine and Cellular Longevity

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Cardiotoxicity as an off-target effect of doxorubicin therapy is a major limiting factor for its clinical use as a choice cytotoxic agent. Seeds of Irvingia gabonensis have been reported to possess both nutritional and medicinal values which include antidiabetic, weight losing, antihyperlipidemic, and antioxidative effects. Protective effects of Irvingia gabonensis ethanol seed extract (IGESE) was investigated in doxorubicin (DOX)-mediated cardiotoxicity induced with single intraperitoneal injection of 15 mg/kg of DOX following the oral pretreatments of Wistar rats with 100-400 mg/kg/day of IGESE for 10 days, using serum cardiac enzyme markers (cardiac troponin I (cTI) and lactate dehydrogenase (LDH)), cardiac tissue oxidative stress markers (catalase (CAT), malonyldialdehyde (MDA), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione peroxidase (GSH-Px), and reduced glutathione (GSH)), and cardiac histopathology endpoints. In addition, both qualitative and quantitative analyses to determine IGESE’s secondary metabolites profile and its in vitro antioxidant activities were also conducted. Results revealed that serum cTnI and LDH were significantly elevated by the DOX treatment. Similarly, activities of tissue SOD, CAT, GST, and GSH levels were profoundly reduced, while GPx activity and MDA levels were profoundly increased by DOX treatment. These biochemical changes were associated with microthrombi formation in the DOX-treated cardiac tissues on histological examination. However, oral pretreatments with 100-400 mg/kg/day of IGESE dissolved in 5% DMSO in distilled water significantly attenuated increases in the serum cTnI and LDH, prevented significant alterations in the serum lipid profile and the tissue activities and levels of oxidative stress markers while improving cardiovascular disease risk indices and DOX-induced histopathological lesions. The in vitro antioxidant studies showed IGESE to have good antioxidant profile and contained 56 major secondary metabolites prominent among which are γ-sitosterol, Phytol, neophytadiene, stigmasterol, vitamin E, hexadecanoic acid and its ethyl ester, Phytyl palmitate, campesterol, lupeol, and squalene. Overall, both the in vitro and in vivo findings indicate that IGESE may be a promising prophylactic cardioprotective agent against DOX-induced cardiotoxicity, at least in part mediated via IGESE’s antioxidant and free radical scavenging and antithrombotic mechanisms.

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Section: Discussionmentioning

confidence: 99%

Irvingia gabonensis Seed Extract: An Effective Attenuator of Doxorubicin-Mediated Cardiotoxicity in Wistar Rats

Olorundare

Adeneye

Akinsola

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…However, a recent study showed doxorubicin had vascular toxicity and increase the chance of thrombus formation [125]. In this case, treating the restenosis patients with doxorubicin could have high risk of side effects.…”

Section: Theranostic Nanoparticles For Vascular Injury and Restenosismentioning

confidence: 96%

Recent Advances in the Development of Theranostic Nanoparticles for Cardiovascular Diseases

Vazquez-Prada

Liu

et al. 2021

Nanotheranostics

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Cardiovascular disease (CVD) is the leading cause of death worldwide. CVD includes a group of disorders of the heart and blood vessels such as myocardial infarction, ischemic heart, ischemic injury, injured arteries, thrombosis and atherosclerosis. Amongst these, atherosclerosis is the dominant cause of CVD and is an inflammatory disease of the blood vessel wall. Diagnosis and treatment of CVD remain the main challenge due to the complexity of their pathophysiology. To overcome the limitations of current treatment and diagnostic techniques, theranostic nanomaterials have emerged. The term "theranostic nanomaterials" refers to a multifunctional agent with both therapeutic and diagnostic abilities. Theranostic nanoparticles can provide imaging contrast for a diversity of techniques such as magnetic resonance imaging (MRI), positron emission tomography (PET) and computed tomography (CT). In addition, they can treat CVD using photothermal ablation and/or medication by the drugs in nanoparticles. This review discusses the latest advances in theranostic nanomaterials for the diagnosis and treatment of CVDs according to the order of disease development. MRI, CT, near-infrared spectroscopy (NIR), and fluorescence are the most widely used strategies on theranostics for CVDs detection. Different treatment methods for CVDs based on theranostic nanoparticles have also been discussed. Moreover, current problems of theranostic nanoparticles for CVDs detection and treatment and future research directions are proposed.

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“…The promise of such an approach is evident in studies involving chemotherapy drug (e.g., doxorubicin) encapsulation in actual platelets for tumor‐targeted delivery in lymphoma 102,103 . However, studies have also shown that doxorubicin can directly impact platelet activation and functions leading to thrombotic and thrombocytopenic side effects 104,105 . This provides a strong rationale to use platelet‐mimetic nanoparticles as potential carrier platforms for doxorubicin and other drugs to avoid effects on endogenous platelets while enabling targeted delivery to cancer cells.…”

Section: Platelet‐inspired Nanomedicine Approaches For Treating Cancermentioning

confidence: 99%

Beyond the thrombus: Platelet‐inspired nanomedicine approaches in inflammation, immune response, and cancer

Desai

Koupenova

Machlus

et al. 2022

Journal of Thrombosis and Haemostasis

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The traditional role of platelets is in the formation of blood clots for physiologic (e.g., in hemostasis) or pathologic (e.g., in thrombosis) functions. The cellular and subcellular mechanisms and signaling in platelets involved in these functions have been extensively elucidated and new knowledge continues to emerge, resulting in various therapeutic developments in this area for the management of hemorrhagic or thrombotic events. Nanomedicine, a field involving design of nanoparticles with unique biointeractive surface modifications and payload encapsulation for diseasetargeted drug delivery, has become an important component of such therapeutic development. Beyond their traditional role in blood clotting, platelets have been implicated to play crucial mechanistic roles in other diseases including inflammation, immune response, and cancer, via direct cellular interactions, as well as secretion of soluble factors that aid in the disease microenvironment. To date, the development of nanomedicine systems that leverage these broader roles of platelets has been limited. Additionally, another exciting area of research that has emerged in recent years is that of platelet-derived extracellular vesicles (PEVs) that can directly and indirectly influence physiological and pathological processes. This makes PEVs a unique paradigm for platelet-inspired therapeutic design. This review aims to provide mechanistic insight into the involvement of platelets and PEVs beyond hemostasis and thrombosis, and to discuss the current state of the art in the development of platelet-inspired therapeutic technologies in these areas, with an emphasis on future opportunities.

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Doxorubicin contributes to thrombus formation and vascular injury by interfering with platelet function

Cited by 17 publications

References 49 publications

Irvingia gabonensis Seed Extract: An Effective Attenuator of Doxorubicin-Mediated Cardiotoxicity in Wistar Rats

Irvingia gabonensis Seed Extract: An Effective Attenuator of Doxorubicin-Mediated Cardiotoxicity in Wistar Rats

Recent Advances in the Development of Theranostic Nanoparticles for Cardiovascular Diseases

Beyond the thrombus: Platelet‐inspired nanomedicine approaches in inflammation, immune response, and cancer

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