Protective effect of valsartan against doxorubicin-induced cardiotoxicity: Histopathology and metabolomics in vivo study.

Autor: Alhazzani K; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Alotaibi MR; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Alotaibi FN; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Aljerian K; Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia., As Sobeai HM; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Alhoshani AR; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Alanazi AZ; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Alanazi WA; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Alswayyed M; Department of Pathology and Laboratory Medicine, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia.
Jazyk: angličtina
Zdroj: Journal of biochemical and molecular toxicology [J Biochem Mol Toxicol] 2021 Sep; Vol. 35 (9), pp. e22842. Date of Electronic Publication: 2021 Jul 17.
DOI: 10.1002/jbt.22842
Abstrakt: Doxorubicin (DOX) treatment has been associated with cardiotoxicity. Therefore, it is crucial to search for a therapeutic that can effectively mitigate DOX-induced cardiotoxicity. This study was conducted to investigate the protective effects of valsartan (VAL) against DOX-induced cardiotoxicity. Sprague-Dawley rats were divided into four treatment groups: Group I: Control, Group II: VAL (30 mg/kg, ip), Group III: DOX (15 mg/kg, ip), and Group IV: VAL + DOX (30 + 15 mg/kg, ip). All groups were treated every other day for 14 days. Blood was isolated for biochemical and metabolomics studies, and sections of the heart were also analyzed for histopathological and immunohistochemical alterations to detect changes in P53, BAX, BCL-2, and P62 expression. The combination of VAL + DOX resulted in a marked decrease in cardiac biomarker enzymes (aminotransferase and creatine phosphokinase) compared to DOX monotherapy. In addition, the histopathological examination of the VAL + DOX combination revealed a low percentage of fibrosis and inflammation. Immunohistochemical expression of p53 and BAX was significantly reduced, whereas BCL-2 expression was significantly increased in the VAL + DOX treatment group compared to DOX monotherapy. Also, the combination of VAL + DOX reverses the negative effect of DOX on nuclear p62 expression. Analysis of serum metabolites showed that DOX monotherapy reduced the number of several amino acids, whereas the combination of VAL + DOX restored these metabolic pathways. This study revealed the potential cardioprotective effect of VAL, which may provide novel and promising approaches for managing cardiotoxicity induced by DOX.
(© 2021 Wiley Periodicals LLC.)
Databáze: MEDLINE
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