scholarly journals 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

Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 886
Author(s):  
Samar S. Elblehi ◽  
Yasser S. El-Sayed ◽  
Mohamed Mohamed Soliman ◽  
Mustafa Shukry

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.

2015 ◽  
Vol 34 (2) ◽  
pp. 151-161 ◽  
Author(s):  
Alan H. Stokes ◽  
J. Greg Falls ◽  
Lawrence Yoon ◽  
Neal Cariello ◽  
Brenda Faiola ◽  
...  

Cardiovascular (CV) safety concerns are among the leading causes of compound attrition in drug development. This work describes a strategy of applying novel end points to a 7-day rodent study to increase the opportunity to detect and characterize CV injury observed in a longer term (ie, 28 days) study. Using a ghrelin receptor agonist (GSK894281), a compound that produces myocardial degeneration/necrosis in rats after 28 days at doses of 0.3, 1, 10, or 60 mg/kg/d, we dosed rats across a range of similar doses (0, 0.3, 60, or 150 mg/kg/d) for 7 days to determine whether CV toxicity could be detected in a shorter study. End points included light and electron microscopies of the heart; heart weight; serum concentrations of fatty acid-binding protein 3 (FABP3), cardiac troponin I (cTnI), cardiac troponin T (cTnT), and N-terminal proatrial natriuretic peptide (NT-proANP); and a targeted transcriptional assessment of heart tissue. Histologic evaluation revealed a minimal increase in the incidence and/or severity of cardiac necrosis in animals administered 150 mg/kg/d. Ultrastructurally, mitochondrial membrane whorls and mitochondrial degeneration were observed in rats given 60 or 150 mg/kg/d. The FABP3 was elevated in rats given 150 mg/kg/d. Cardiac transcriptomics revealed evidence of mitochondrial dysfunction coincident with histologic lesions in the heart, and along with the ultrastructural results support a mechanism of mitochondrial injury. There were no changes in cTnI, cTnT, NT-proANP, or heart weight. In summary, enhancing a study design with novel end points provides a more integrated evaluation in short-term repeat dose studies, potentially leading to earlier nonclinical detection of structural CV toxicity.


2018 ◽  
Vol 13 (2) ◽  
pp. 47-53
Author(s):  
Sharmin Nahar ◽  
Qazi Shamima Akhter

Background: The prevalence of myocardial infarction (MI) is increasing day by day in Bangladesh due to socioeconomic transition. Spices and herbs are important source of remedy for various diseases in human. Curcuma longa suggested to be used as an indigenous medicine for the prevention and treatment of cardiovascular disease. Objective: To observe the effect of Curcuma longa in isoproterenol induced myocardial infarction in Wistar albino rats. Methods: This experimental study was carried out in the Department of Physiology, Dhaka Medical College, Dhaka during 2015. Twenty one Wistar albino male rats, weighing 100 to 150 g (initial body weight); aged 85 to 100 days were selected for the study. After acclimatization for 14 days, the rats were divided into BC (Baseline control group), ISP-TC (Isoproterenol treated control group) and CLP-ISPT (Curcuma longa pretreated and isoproterenol treated group). Each group consisted of 7 rats. After experiment, on the 10th day, final body weight was taken, rats were sacrificed and blood samples were collected from the heart. The heart was removed and weighed. Serum creatine kinase-MB (CK-MB) level was estimated by ELISA method and Troponin I (cTnI) level by AxSYM method. The statistical analysis was done by one way ANOVA and Bonferroni test as applicable. Results: In this study, the mean percent (%) change of body weight (p<0.01), mean serum CK-MB (p<0.001) and cTnI (p<0.001) levels were significantly higher but mean heart weight was non significantly higher in ISP-TC in comparison to those of BC. Again, the mean percent (%) change of body weight (p<0.01), mean heart weight (p<0.01), mean serum CK-MB (p<0.01) and cTnI (p<0.001) levels were significantly lower in CLP-ISPT than those of ISP-TC group. Conclusion: From the results, it can be concluded that Curcuma longa may have cardioprotective effect. J Bangladesh Soc Physiol. 2018, December; 13(2): 47-53


1999 ◽  
Vol 45 (12) ◽  
pp. 2296-2297 ◽  
Author(s):  
Wim G Meijer ◽  
Joost CJM Swaanenburg ◽  
DirkJan van Veldhuisen ◽  
Ido P Kema ◽  
Pax HB Willemse ◽  
...  

2011 ◽  
Vol 152 (38) ◽  
pp. 1528-1534 ◽  
Author(s):  
Eszter Szánthó ◽  
Zoltán Szabó ◽  
József Varga ◽  
György Paragh ◽  
Anna V. Oláh

Troponin is the first choice in the diagnosis of acute myocardial infarction. Correct interpretation is challenging, because high sensitive troponin tests used today detect even the smallest cardiac damage. Methods: High sensitive troponin T (Roche) and troponin I (Mitsubishi Pathfast) and creatine-kinase activity were measured in 20 patients, each having two samples with the time lapse 3–9 hours. Results: In the group without acute myocardial infarction (n = 10) no significant increase in creatine-kinase and creatine-kinase-MB levels were seen, and the mild raise of troponins was due to other cardiovascular problems (atrial fibrillation, paroxysmal supraventricular tachycardia). With acute myocardial infarction (n = 10) a dramatic increase of troponin levels was found in the second samples, and also an increase of creatine-kinase and creatine-kinase-MB activity. According to Fischer-probe a twofold or higher increase of troponin implies 19-times higher risk of acute myocardial infarction in the case of troponin T and 8-times odds ratio at troponin I. Conclusions: The patient’s accompanying diseases should always be considered. If the troponin level is elevated, the measurement should be repeated within 3–6 hours. When troponin shows at least a twofold increase and the patient has chest pain or positive ECG, AMI is likely, and the patient needs special medical care. Although the first troponin level might be elevated if accompanying diseases cause chronic cardiac damage, it can be differentiated by a second troponin measurement. Orv. Hetil., 2011, 152, 1528–1534.


2015 ◽  
Vol 156 (24) ◽  
pp. 964-971
Author(s):  
Ferenc Kovács ◽  
Ibolya Kocsis ◽  
Marina Varga ◽  
Enikő Sárváry ◽  
György Bicsák

Introduction: Cardiac biomarkers have a prominent role in the diagnosis of acute myocardial infarction. Aim: The aim of the authors was to study the diagnostic effectiveness of automated measurement of cardiac biomarkers. Method: Myeloperoxidase, high-sensitivity C-reactive protein, myoglobin, heart-type fatty acid binding protein, creatine kinase, creatine kinase MB, high-sensitivity troponin I and T were measured. Results: The high-sensitivity troponin I was the most effective (area under curve: 0.86; 95% confidence interval: 0.77–0.95; p<0.001) for the diagnosis of acute myocardial infarction. Considering a critical value of 0.35 ng/mL, its sensitivity and specificity were 81%, and 74%, respectively. Combined evaluation of the high-sensitivity troponin T and I, chest pain, and the electrocardiogram gave the best results for separation of acute myocardial infarction from other diseases (correct classification in 62.5% and 98.9% of patients, respectively). Conclusions: Until a more sensitive and specific cardiac biomarker becomes available, the best method for the diagnosis of acute myocardial infarction is to evaluate electrocardiogram and biomarker concentration and to repeat them after 3–6 hours. Orv. Hetil., 2015, 156(24), 964–971.


1999 ◽  
Vol 29 (2) ◽  
pp. 93-101 ◽  
Author(s):  
K. Penttilä ◽  
H. Koukkunen ◽  
A. Kemppainen ◽  
M. Halinen ◽  
T. Rantanen ◽  
...  

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