Mesenchymal stem cells pretreated with platelet-rich plasma modulate doxorubicin-induced cardiotoxicity

Abstract

<jats:p> The cardiotoxic adverse effect of doxorubicin (DOX) is the major factor limiting its use. Recently, mesenchymal stem cells (MSCs) have been implicated in the preclinical studies of treatment of DOX-induced cardiotoxicity. The question is MSCs pretreated with platelet-rich plasma (PRP) have a better influence on DOX-induced cardiotoxicity compared to the influence of MSCs alone. Twenty-four Wistar rats were categorized into control, DOX-treated, MSC-treated, and PRP/MSC-treated groups. DOX was injected for two consecutive weeks. Light microscopic, biochemical markers (interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-α), and creatine kinase-MB (CK-MB)), immunohistochemical (Bax, Bcl2, vascular endothelial growth factor (VEGF), and cardiac troponin-I (CT-I)), and oxidative/antioxidative markers (malondialdehyde (MDA)/superoxide dismutase (SOD)) were measured. Degenerative cardiac changes were detected in the DOX-treated group with complete loss of the architecture and coagulative necrosis. These changes were accompanied with the elevation of the serum level of CK-MB and loss of CT-I immunoreactivity. The major factors in the DOX-induced cardiotoxicity were the oxidative stress (elevated MDA/decreased SOD), inflammation (elevated TNF-α/decreased IL-10), and cardiac apoptosis (lower Bcl2, higher Bax, and lower Bcl2/Bax ratio). MSCs and PRP/MSCs attenuate DOX-induced cardiotoxicity. Better attenuation was observed in the PRP/MSC-treated group. PRP/MSC combination reduced greatly the MDA and TNF-α and increased IL-10, Bcl2/Bax ratio, and VEGF. PRP had no significant influence over the Bcl2, Bax, and SOD. In conclusion, DOX in its toxic dose induced myocardial injury. This destructive effect is related to oxidative stress, inflammation, and cardiac apoptosis. PRP/MSC possesses a better attenuation over the DOX-induced toxicity compared to MSC alone. </jats:p>

Date Palm Pollen Extract Avert Doxorubicin-Induced Cardiomyopathy Fibrosis and Associated Oxidative/Nitrosative Stress, Inflammatory Cascade, and Apoptosis-Targeting Bax/Bcl-2 and Caspase-3 Signaling Pathways

“…Opened mitochondrial pores lead to mitochondrial cytochrome-C release, and activated caspase-3 triggers proteolytic degradation of cellular components death [127]. Herein, the immunohistochemical staining of myocardial tissues showed that DOX caused an increase in the cleaved caspase-3 and Bax expressions and decreased Bcl-2 expression, which reflected apoptosis's role in DOX-induced cardiomyopathy [76,86,128]. Nevertheless, pre-cotreatment with DPPE reduced cleaved caspase-3 and Bax and enhanced Bcl-2 expressions, implying that DPPE's anti-apoptotic activity could conserve myocardial integrity and mitigate myocardial damage.…”

Keap1/Nrf2 pathway in sodium fluoride-induced cardiac toxicity and the prophylactic role of vitamin C versus platelet-rich plasma

“…The investigation revealed hyperemia of interstitial vessels, hyaline degeneration andZenker's necrosis in muscle fibers and mononuclear cell. A study done by Basha and Sujitha, The heart is vulnerable to oxidative stress due to the abundance of mitochondria; the site of basal ROS generation and due to its inherent low antioxidant defenses [51]. Vitamin C is an electron donor, and this is the basis of all its known functions.…”

“…Zaki et al, [51] revealed that the modulatory effect of mesenchymal stem cells (MSCs) pretreated with platelet-rich plasma (PRP) on doxorubicin (DOX)-induced cardiotoxicity was superior to the modulatory effect of MSCs alone. The authors mentioned that oxidative stress underlies the DOX-induced cardiotoxicity and accordingly found the oxidant marker MDA to be elevated, while the antioxidant marker SOD decreased in DOX-treated groups.…”

Stem cells: a new way of therapy for cardiovascular disorders

“…An improvement of 40.44 m in 6MWT and in NYHA and LVEF groups 95% and 5.25% reduction is observed (3). Moreover, MSC's treated with plateletrich plasma has a greater influence than MSC's alone (12). Vesicles derived from MSC's are used for the treatment of many disorders (13).…”