Purpose: To explore the protective and curative effects of molsidomine (MOL) on doxorubicin (DOX)-induced cardiac damage in the in vivo rat heart.
Methods: Forty rats were randomized into five groups (n = 8): (1) the control group; (2) the MOL group (10 mg/kg for 21 days); (3) the DOX group (a single dose of 20 mg/kg); (4) the DOX + MOL group (3 days after the single dose of DOX, 10 mg/kg MOL continued for 21 days), and (5) the MOL + DOX group (24 h after a 21-day regimen of 10 mg/kg MOL, a single dose of DOX). The rats were monitored for mean arterial blood pressure, heart rate, O2 saturation, and electrocardiography. Heart tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and nitric oxide (NO) were determined.
Results: Blood pressure and O2 saturation values indicated a significant decrease in the DOX group compared with the control group. T negativity was observed in 4 of 8 rats in the DOX group, in 1 of 8 rats in the DOX + MOL group, and in 4 of 8 rats in the MOL + DOX group. MDA levels were significantly higher in the DOX group. SOD, GSH, and NO levels were significantly lower in the DOX group compared with the other groups. There was no statistically significant difference in the CAT levels in any of the study groups compared with controls. DOX treatment induced morphological alterations, such as disorganization of cardiomyocytes, loss of myofibrils, and cytoplasmic vacuolization in the heart. On the other hand, histological damage was significantly reduced in the DOX + MOL and MOL + DOX groups.
Conclusion: This study implies that there are cardioprotective effects of MOL on DOX-induced cardiotoxicity.
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http://dx.doi.org/10.1159/000354807 | DOI Listing |
Curr Cancer Drug Targets
January 2025
Department of Cardiology, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, Liaoning, China.
Introduction: The cardiotoxicity and subsequent Heart Failure (HF) induced by Doxorubicin (DOX) limit the clinical application of DOX. Valsartan (Val) is an angiotensin II receptor blocker that could attenuate the HF induced by DOX. However, the underlying mechanism of Val in this process is not fully understood.
View Article and Find Full Text PDFJ Toxicol Environ Health A
January 2025
Laboratory of Experimental Cancerology (LabCancer), Department of Biophysics and Physiology, Federal University of Piauí, Teresina-PI, Brazil.
The chemotherapeutic drug doxorubicin (DOX) has been widely used for treating solid tumors attributed to its antiproliferative effectiveness; however, its clinical use is limited due to side effects, including cardiotoxicity, myelosuppression, and drug resistance. Combining DOX with buthionine sulfoximine (BSO), a glutathione (GSH) synthesis inhibitor, showed promising results in overcoming these adverse effects, potentially reducing the required DOX dose while maintaining efficacy. The aim of the present study was to examine the effects of different concentrations of BSO and DOX, both individually and in combination, utilizing B16/F10 (murine melanoma), SNB-19 (human glioblastoma), S180 (murine sarcoma), and SVEC4-10 (murine endothelial) cell lines.
View Article and Find Full Text PDFToxicol Rep
June 2025
Therapeutic Chemistry Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, El Buhouth St., Dokki, Cairo 12622, Egypt.
Doxorubicin (DOX) is a powerful antineoplastic FDA-approved anthracycline-derived antibiotic and is considered as the most suitable intervention for solid tumors and hematological cancers therapy. However, its therapeutic application is highly limited due to acute and chronic renal, hematological and testicular toxicity. Oxidative stress, lipid peroxidation and apoptosis in germ cells as well as low sperm count, motility and disturbing steroidogenesis are the principal machineries of DOX-induced testicular toxicity.
View Article and Find Full Text PDFCardiovasc Toxicol
January 2025
Chair and Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Banacha 1b, 02-097, Warsaw, Poland.
Doxorubicin (DOX) is an important drug used in the treatment of many malignancies. Unfortunately DOX causes various side effects, with cardiotoxicity being the most characteristic. Risk factors for DOX induced cardiotoxicity (DIC) include cumulative dose of DOX, preexisting cardiovascular diseases, dyslipidemia, diabetes, smoking, along with the use of other cardiotoxic agents.
View Article and Find Full Text PDFChin J Integr Med
January 2025
Department of Cardiovascular Medicine, National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
Objective: To explore the molecular mechanism of Shenmai Injection (SMI) against doxorubicin (DOX) induced cardiomyocyte apoptosis.
Methods: A total of 40 specific pathogen-free (SPF) male Sprague Dawley (SD) male rats were divided into 5 groups based on the random number table, including the control group, the model group, miR-30a agomir group, SMI low-dose (SMI-L) group, and SMI high-dose (SMI-H) group, with 8 rats in each group. Except for the control group, the rats were injected weekly with DOX (2 mg/kg) in the tail vein for 4 weeks to induce myocardial injury, and were given different regimens of continuous intervention for 2 weeks.
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