Cardioprotective Effect of Rheum turkestanicum Against Doxorubicin-Induced Toxicity in Rats

• Published in: Frontiers in pharmacology 2022-06, Vol.13
• Main Authors: Hosseini, Azar, Safari, Mohammad-Kazem, Rajabian, Arezoo, Boroumand-Noughabi, Samaneh, Eid, Ali H., Al Dhaheri, Yusra, Gumpricht, Eric, Sahebkar, Amirhossein
• Format: Article
• Language: English
• Subjects: cardiotoxicity; chemotherapy; doxorubicin; herbal medicine; oxidative stress; Pharmacology; Rheum turkestanicum
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2022.909079

Background: Doxorubicin as an anti-cancer drug causes cardiotoxicity, limiting its tolerability and use. The mechanism of toxicity is due to free radical production and cardiomyocytes injury. This research evaluated Rheum turkestanicum ( R.turkestanicum ) extract against doxorubicin cardiotoxicity due to its considerable in vitro antioxidant activity. Methods: Male Wistar rats received 2.5 mg/kg doxorubicin intraperitoneally every other day for 2 weeks to create an accumulative dose. R. turkestanicum was administrated at a dose of 100 and 300 mg/kg intraperitoneally from the second week for 7 days. On the 15th day, the animals were anesthetized and blood was collected from cardiac tissue for evaluation of alanine aminotransferase (ALT), cardiac muscle creatinine kinase (CK-MB), troponin T (cTn-T), lactate dehydrogenase (LDH), and B-type natriuretic peptide brain natriuretic peptide. A cardiac homogenate was also collected to determine superoxide dismutase (SOD), catalase Catalase Activity, malondialdehyde (MDA), and thiols. Histopathology was also performed. Results: Doxorubicin increased all cardiac enzymes and malondialdehyde, correlating with a reduction in SOD, catalase, and thiols. Histopathology revealed extracellular edema, moderate congestion, and hemorrhage of foci. In contrast, administration of R. turkestanicum ameliorated these doxorubicin-induced pathophysiological changes. Conclusion: This study revealed that the extract ameliorated doxorubicin-induced cardiac toxicity via modulation of oxidative stress-related pathways. Liquid chromatography-mass spectrometry analysis of R. turkestanicum indicated several components with potent pharmacological properties.