Alginate oligosaccharide alleviates myocardial reperfusion injury by inhibiting nitrative and oxidative stress and endoplasmic reticulum stress-mediated apoptosis

摘要

Alginate oligosaccharide (AOS) has recently demonstrated the ability to protect against acute doxorubicin cardiotoxicity and neurodegenerative disorders by inhibiting oxidative stress and endoplasmic reticulum (ER) stress-mediated apoptosis, which are both involved in myocardial ischemia/reperfusion (I/R) injury. In the present study, we investigated whether pretreatment with AOS protects against myocardial I/R injury in mice and explored potential cardioprotective mechanisms. AOS pretreatment significantly decreased the infarct size, reduced the cardiac troponin-I concentration, and ameliorated the cardiac dysfunction. Accompanied with the reduced cardiac injury, AOS pretreatment clearly decreased I/R-induced myocardial apoptosis. With regard to mechanism, AOS pretreatment markedly attenuated nitrative/oxidative stress, as evidenced by decreases in 3-nitrotyrosine content and superoxide generation, and downregulated inducible nitric oxide synthase, NADPH oxidase2, and 4-hydroxynonenal. Moreover, AOS pretreatment decreased myocardial apoptosis by inhibiting the ER stress-mediated apoptosis pathway, which is reflected by the downregulation of C/EBP homologous protein, glucose-regulated protein 78, caspase-12, and Bcl-2-associated X protein, and by the upregulation of the anti-apoptotic protein B-cell lymphoma-2. Collectively, these findings demonstrate that AOS renders the heart resistant to I/R injury, at least in part, by inhibiting nitrative/oxidative stress and ER stress-mediated apoptosis.