H2S improves doxorubicin-induced myocardial fibrosis by inhibiting oxidative stress and apoptosis via Keap1-Nrf2.

OBJECTIVE

We waimed to investigate whether H2S can relieve the myocardial fibrosis caused by doxorubicin through Keap1-Nrf2.

METHODS

Sprague-Dawley (SD) rats were randomly divided into four groups: normal control group (Control); DOX model group (DOX); H2S intervention model group (DOX+H2S); H2S control group (H2S). DOX and DOX+H2S group were injected with doxorubicin (3.0 mg/kg/time) intraperitoneally. Both of the Control group and H2S groups were given normal saline in equal volume, 2 weeks later, DOX+H2S and H2S group were controlled with NaHS (56 μmol/kg/d) through the abdominal cavity, while the Control and DOX group were injected with normal saline of the same dosage intraperitoneally.

RESULTS

Myocardial injury and myocardial cell apoptosis were significantly increased, the H2S content in myocardial tissue was remarkably down-regulated, the expression levels of MDA, Keap1, caspase-3, caspase-9, TNF-α, IL1β, MMPs and TIMP-1 in rat myocardial tissue was significantly up-regulated (P< 0.05), and the expression levels of GSH, NQO1, Bcl-2 were down-regulated compared with those of control group. The above results can be reversed by the DOX+H2S group. There is no statistically significant difference between the Control group and the H2S control group.

CONCLUSIONS

These results suggest that H2S can improve DOX-induced myocardial fibrosis in rats, and the keap1/Nrf2 signaling pathway, oxidative stress, inflammation, and apoptosis may be involved in the mechanism.