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The protective effect of losartan against sorafenib induced cardiotoxicity: Ex-vivo isolated heart and metabolites profiling studies in rat.
Metadata
Journaleuropean journal of pharmacology3.263Date
2020 Jun 04
4 months ago
Type
Journal Article
Volume
2020-Sep-05 / 882 : 173229
Author
Abdelgalil AA 1, Mohamed OY 2, Ahamad SR 3, Al-Jenoobi FI 4
Affiliation
  • 2. Department of Pharmacology, College of Medicine, King Saud University, Saudi Arabia.
  • 3. Central Laboratory, College of Pharmacy, King Saud University, Saudi Arabia; Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Saudi Arabia.
  • 4. Department of Pharmaceutics, College of Pharmacy, King Saud University, Saudi Arabia.
Doi
PMIDMESH
Abstract
Sorafenib, a tyrosine kinase inhibitor that is used in the treatment of hepatocellular and renal cell carcinoma, was reported to induce cardiotoxicity. This study aimed to investigate the potential cardioprotective effect of losartan against sorafenib-induced cardiotoxicity in rat. Sorafenib significantly reduced the left ventricular pressure, heart rate dp/dt max & dp/dt min (indexes of myocardial contractility and relaxation; respectively), and prolonged both the systolic and diastolic periods. Coadminstration of losartan significantly reversed the effects of sorafenib on heart rate, dp/dt max and dp/dt min. In addition, there was a tendency for losartan to reverse sorafenib reduction in left ventricular pressure and perfusion pressure but it did not reach statistical significance. A GC-MS non-targeted based metabolites profiling of rat plasma revealed elevated metaboites, including urea and fatty acids levels, associated with sorafenib induced cardiotoxicity. However, only glycine and lactic acid were statistically significant. Interestingly, losartan co-administration with sorafenib restored these changes, and resulted in a significantly reduced glycine, urea and some fatty acids levels namely; Cis-vaccenic acid, oleic acid, stearic acid and undecanoic acid. In addition, based on histology results, losartan coadminitration almost obviated sorafenib-induced changes in cardiac tissues. The study suggests that losartan has the potential to exert a protective effect against sorafenib-induced cardiotoxicity.
Keywords: Cardiotoxicity Isolated heart Losartan Metabolomics Sorafenib
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3.3
Eur J Pharmacoleuropean journal of pharmacology
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LocationNetherlands
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