Scutellarin protects against doxorubicin-induced acute cardiotoxicity and regulates its accumulation in the heart

Abstract

The clinical use of doxorubicin (DOX) is limited by its dose-dependent cardiotoxicity. The present study investigated the effects of scutellarin against DOX-induced cardiotoxicity in rats using pharmacodynamic and pharmacokinetic approaches. DOX (20 mg/kg) was injected intraperitoneally (i.p.) as a single dose, and scutellarin (5 mg/kg/day) was injected intravenously (i.v.) for 3 days. Rats treated with DOX showed acute cardiotoxicity as indicated by the elevated serum lactate dehydrogenase (LDH) activity (4057.8 ± 107.2 vs. 2032.7 ± 70.95), tissue malondialdehyde (MDA) level (2.083 ± 0.10 vs. 1.103 ± 0.09), cardiac troponin T (cTnT) concentration (0.1695 ± 0.0114 ng/mL), the decreased left ventricular ejection fraction (LVEF) (47.75 ± 15.79 vs. 78.72 ± 7.25) and left ventricular fractional shortening (LVFS) (20.66 ± 8.06 vs. 43.7 ± 6.76) compared with those of the control group. Cotreatment with scutellarin significantly decreased the LDH activity (2595.9 ± 72.73), MDA level (1.380 ± 0.06), cTnT concentration (0.0222 ± 0.0041 ng/m L), increased LVEF (76.70 ± 3.91) and LVFS (40.28 ± 3.68). Histopathological studies showed disruption of cardiac tissues in the DOX groups. Cotreatment with scutellarin reduced the damage to cardiac tissues. In the pharmacokinetic and tissue distribution study, scutellarin reduced the heart tissue exposure to DOX but did not change the AUC of plasma. These results suggest that scutellarin can protect against DOX-induced acute cardiotoxicity through its antioxidant activity and alterations of heart concentrations.

Dietary Glycine Prevents FOLFOX Chemotherapy-Induced Heart Injury: A Colorectal Cancer Liver Metastasis Treatment Model in Rats

“…Besides the FOLFOX-induced pathologic changes in the myocardial tissue, impaired LV function was detected and the decrease of LVEF after FOLFOX correlated to h-FABP level and myocardial fibrosis. These results are in accordance with several recent preclinical studies, which also showed an increased level of apoptosis, myocardial fibrosis, and decreased LVEF after treatment with anthracycline-based chemotherapy [35][36][37][38] and with the series of reports that showed reduced LVEF following 5-FU-based chemotherapy in humans [39][40][41][42][43].…”

Protective role of ginseng extract against oxidative stress, reproductive and some biochemical parameters alterations induced by doxorubicin in male rats

“…Similar results were observed in previous studies (Mohamed et al 2015, Faten et al 2018, Haybar et al 2019. Xipeng et al (2017) showed that doxorubicin increased MDA coupled with reduction in SOD, CAT, GSH and GSH-Px in rats. These findings may be attributed to the generation of free radicals and the induction of oxidative stress induced by doxorubicin administration (El-Maddawya & Abdel-Naby 2019, Injac et al 2008).…”

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“…DISCUSSION: Doxorubicin belongs to the group of anthracyclines which were introduced for the use of cancer treatment in the late 1960s and remained one of the most commonly prescribed anticancer drugs 7,20 . However, its dose-dependent cardiotoxicity limits the efficacy as an antitumor treatment.…”

“…In the present study, for the estimation of cardiotoxicity, blood samples and tissue samples were collected after three days of doxorubicin administration. The three-day time-point was selected based on data from pharmacokinetic studies showing that the average terminal half-life of doxorubicin lies between 12 and 48 h and because acute cardiotoxicity appears between 48 and 72 h 20 . In cardiomyocyte damage, usually, cTnI concentration increases in blood 3-7 h after cell damage reaches to maximum level 10-20 h and returns to normal value within 10 days 34 .…”