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Published on: May 16, 2020
[Metallothionein inhibited DOX-induced cardiac apoptosis in mice]
Yi Shuai1, Jun Guo, Shuang-qing Peng
1Beijing Institute of Pharmacology and Toxicology, National Beijing Center for Drug Safety Evaluation and Research, Beijing 100850, China.
Objective:
To investigate the inhibitive effect of metallothionein (MT) on DOX-induced cardiac apoptosis and the involved possible mechanisms.
Methods:
Adult male C57BL mice (6-8 weeks old) were randomly assigned into four groups and given the following treatment: Zinc (ZnSO4, 300 micromol/kg, s.c., once a day for 2 days) or equal volume of physiological saline prior to a single dose of DOX (15 mg/kg, i.p.) or equal volume of saline. Animals were sacrificed on the 4th day after DOX administration and hearts were excised for further studies, including cadmium-hemoglobin affinity assay for MT concentration, ELISA detection of DNA fragmentation and Western blot analysis of Bax and Bcl-2.
Results:
DOX administration decreased heart weight by 10% and caused remarkable cardiac apoptosis as demonstrated by DNA fragments, while Zinc pretreatment significantly increased the MT levels and therefore inhibited the cardiac apoptotic effect of DOX. Elevated expression of Bax was obviously observed after DOX treatment, while this elevation was prevented by MT induction by Zinc. On the contrary, Bcl-2 protein level was not altered significantly among each group.
Conclusion:
These findings suggest that metallothionein induced by Zinc exhibits protective effects on the cardiac apoptosis of DOX, which might be mediated through the prevention of Bax protein up-regulation by DOX and associated elevation of Bax/Bcl-2 ratio.
