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The cardioprotective effects of 5e were further verified in vivo in
Notes and references
the MI mice model.[20] Mice treated with 5e for 7 days were
subjected to coronary occlusion and the hearts were harvested 72 h
post MI. Infarct size was assessed with TTC staining (2,3,5-
triphenyltetrazolium chloride), this white compound was
enzymatically reduced to red TPF (1,3,5-triphenylformazan) in living
tissues, while it remains as white TTC in areas of infarction since
these enzymes have been degraded due to apoptosis. For this reason,
healthy viable heart muscle will be stained in deep red, while areas
of potential infarctions will be more pale. Infarction size was
calculated as the ratio of scar average circumferences to left
ventricular average inner circumferences. The results showed that
infarct size was significantly larger in post MI mice (Model group)
than that in sham-operated mice (Normal group) (Figure 4a).
Remarkably, donor 5e treatment relived myocardial infarction in a
dose-dependent manner. Low (15 mg/kg/day) and high (30
mg/kg/day) dose of 5e reduce infarction size to 74.75% and 63.97%
of the model group, respectively (Figures 4b-c).
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while massive red fluorescent dots indicating fragments of DNA were
found in heart section of model group. Donor 5e displayed an
obvious benefit in reducing the number of TUNEL-positive cells.
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Figure 5. H&E staining was performed using heart sections to determine the
morphological changes. (a) Normal group; (b) Model group; (c) Treated with 5e, 30
mg/kg/day. Scale bar: 10 μm.
In summary, a series of thioester-based H2S donors were
developed. These donors are stable in aqueous solution, and release
significant amounts of H2S in a slow and controllable manner in the
presence of Cys. The most potent donor 5e exhibited promising
cardioprotective activity against H2O2-induced oxidative stress by
decreasing the mitochondrial membrane potential loss and lactate
dehydrogenase release in H9c2 cells. More importantly, donor 5e
also exhibited potent cardioprotective effects in an in vivo
myocardial infarction mice model by reducing myocardial infarct size
and cardiomyoblasts apoptosis. Taken together, our study
demonstrated that the new allyl thioesters may have potential as
cardioprotective agents by releasing H2S.
Acknowledgements
19 L. Wang, H. Huang, Y. Fan, B. Kong, H. Hu, K. Hu, J. Guo, Y. Mei,
W. L. Liu, Oxid. Med. Cell. Longev. 2014, 2014, 960362.
20 S.S. Luo, X.F. Gu, F.F. Ma, C.H. Liu, Y.Q. Shen, R.W. Ge, Y.Z. Zhu,
Rree Radic. Biol. Med. 2016, 92, 1-14.
We gratefully acknowledge financial support from the National
Natural Science Foundation of China (81673306, 81703348), and
"Double First-Class" University project CPU2018GY04, CPU2018GY35,
China Pharmaceutical University.
4 | J. Name., 2012, 00, 1-3
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