Abstract
Simple SummaryThe use of date palm pollen ethanolic extract (DPPE) is a conventional approach in improving the side-effects induced by Doxorubicin (DOX).DPPE mitigated DOX-induced body and heart weight changes and ameliorated DOX-induced elevated cardiac injury markers. In addition, serum cardiac troponin I concentrations (cTnI), troponin T (cTnT), and N-terminal NBP and cytosolic (Ca+2) were amplified by alleviating the inflammatory and oxidative injury markers and decreasing histopathological lesions severity. DPPE decreased DOX-induced heart injuries by mitigating inflammation, fibrosis, and apoptosis through its antioxidant effect. To reduce DOX-induced oxidative stress injuries and other detrimental effects, a combined treatment of DPPE is advocated.Doxorubicin (DOX) has a potent antineoplastic efficacy and is considered a cornerstone of chemotherapy. However, it causes several dose-dependent cardiotoxic results, which has substantially restricted its clinical application. This study was intended to explore the potential ameliorative effect of date palm pollen ethanolic extract (DPPE) against DOX-induced cardiotoxicity and the mechanisms underlying it. Forty male Wistar albino rats were equally allocated into Control (CTR), DPPE (500 mg/kg bw for 4 weeks), DOX (2.5 mg/kg bw, intraperitoneally six times over 2 weeks), and DPPE + DOX-treated groups. Pre-coadministration of DPPE with DOX partially ameliorated DOX-induced cardiotoxicity as DPPE improved DOX-induced body and heart weight changes and mitigated the elevated cardiac injury markers activities of serum aminotransferases, lactate dehydrogenase, creatine kinase, and creatine kinase-cardiac type isoenzyme. Additionally, the concentration of serum cardiac troponin I (cTnI), troponin T (cTnT), N-terminal pro-brain natriuretic peptide (NT-pro BNP), and cytosolic calcium (Ca+2) were amplified. DPPE also alleviated nitrosative status (nitric oxide) in DOX-treated animals, lipid peroxidation and antioxidant molecules as glutathione content, and glutathione peroxidase, catalase, and superoxide dismutase activities and inflammatory markers levels; NF-κB p65, TNF-α, IL-1β, and IL-6. As well, it ameliorated the severity of histopathological lesions, histomorphometric alteration and improved the immune-staining of the pro-fibrotic (TGF-β1), pro-apoptotic (caspase-3 and Bax), and anti-apoptotic (Bcl-2) proteins in cardiac tissues. Collectively, pre-coadministration of DPPE partially mitigated DOX-induced cardiac injuries via its antioxidant, anti-inflammatory, anti-fibrotic, and anti-apoptotic potential.
Highlights
Doxorubicin (Adriamycin® ), an anthracycline chemotherapeutic medication, has been effective against several types of malignancies since the 1960s [1,2]
Available kits for the measurement of ALT, AST, lactate dehydrogenase (LDH), creatine kinase (CK), CK-MB, GSH, glutathione peroxidase (GPx), CAT and superoxide dismutase (SOD) pursuits, and nitric oxide (NO) and MDA contents were obtained from Biodiagnostic Co. (Cairo, Egypt)
Kits for cardiac troponin I (cTnI) and cTnT levels were gained from MyBiosource, Inc. (San Diego, CA, USA)
Summary
Doxorubicin (Adriamycin® ), an anthracycline chemotherapeutic medication, has been effective against several types of malignancies since the 1960s [1,2] It is the most valuable cytotoxic medication approved by oncologists in tandem with other anti-tumor medications or radiation and surgery [3]. It is highly potent and effective against solid tumors, i.e., breast, lung, bladder, gastrointestinal, thyroid, testicular, and ovarian carcinoma [4,5]. It is used for treating hematological cancers, i.e., Hodgkin’s and non-Hodgkin’s lymphoma and pediatric leukemia [2,3]. The first one is through DNA chelation as DOX interacts with
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