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. 2017 Jul;40(7):875-883.
doi: 10.1007/s12272-017-0907-0. Epub 2017 Mar 17.

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

Xi-Peng Sun  1 , Li-Li Wan  1 , Quan-Jun Yang  1 , Yan Huo  1 , Yong-Long Han  1 , Cheng Guo  2
Affiliations

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

Xi-Peng Sun et al. Arch Pharm Res. 2017 Jul.

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.

Keywords: Cardiotoxicity; Doxorubicin; Oxidative stress; Scutellarin; Tissue distribution.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Effect of DOX and/or scutellarin on the concentration of cTn T in serum. **Compared with DOX-treated group, P < 0.01
Fig. 2
Fig. 2
Effects of DOX alone or combined with scutellarin on LVEF and LVFS of rats. *Compared with DOX-treated group, P < 0.05; **compared with DOX-treated group, P < 0.01
Fig. 3
Fig. 3
Histopathological examination of rat heart (H&E). Control group (a) and SCU-treated group (h) showed normal morphology. DOX-treated group shows myocardial fibrosis, myocardial degeneration and necrosis, inflammatory cell infiltration and occasional vacuolization (b–e). However, only occasional myocardial degeneration and inflammatory cell infiltration was detected in DOX + SCU group (f and g). (white arrow means myocardial fibrosis; white star means myocardial degeneration and necrosis, inflammatory cell infiltration; black arrow means occasional vacuolization)
Fig. 4
Fig. 4
Mean plasma concentration–time curve of DOX along after single dose of 5 mg/kg along or in combination with 5 mg/kg of scutellarin (n = 8)
Fig. 5
Fig. 5
Mean heart concentration–time curve of DOX along after a single dose of 5 mg/kg along or in combination with 5 mg/kg of scutellarin. (n = 6). **Compared with DOX-treated group, P < 0.01
See this image and copyright information in PMC

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