title: Rutin Protects against Pirarubicin-Induced Cardiotoxicity through TGF-β1-p38 MAPK Signaling Pathway.
abstract: We investigated the potential protective effect of rutinum (RUT) against pirarubicin- (THP-) induced cardiotoxicity. THP was used to induce toxicity in rat H9c2 cardiomyoblasts. Positive control cells were pretreated with a cardioprotective agent dexrazoxane (DZR) prior to treatment with THP. Some of the cells were preincubated with RUT and a p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, both individually and in combination, prior to THP exposure. At a dose range of 30-70μM, RUT significantly prevented THP-induced reduction in cell viability; the best cardioprotective effect was observed at a dose of 50μM. Administration of RUT and SB203580, both individually as well as in combination, suppressed the elevation of intracellular ROS, inhibited cell apoptosis, and reversed the THP-induced upregulation of TGF-β1, p-p38 MAPK, cleaved Caspase-9, Caspase-7, and Caspase-3. A synergistic effect was observed on coadministration of RUT and SB203580. RUT protected against THP-induced cardiotoxicity by inhibition of ROS generation and suppression of cell apoptosis. The cardioprotective effect of RUT appears to be associated with the modulation of the TGF-β1-p38 MAPK signaling pathway.
authors.affiliation: Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, China; The Third Hospital Affiliated to The Jinzhou Medical University, No. 5-2 Heping Road, Jinzhou, Liaoning 120001, China.
authors.forename: Yadi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.affiliation: The Third Hospital Affiliated to The Jinzhou Medical University, No. 5-2 Heping Road, Jinzhou, Liaoning 120001, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Tong
authors.affiliation: Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, China.
authors.forename: Liqun
authors.identifier: 0000-0001-8958-330X
authors.initials: L
authors.lastname: Ren