Alginate oligosaccharide pretreatment increased survival, improved cardiac dysfunction, and attenuated myocardial apoptosis in mice with acute doxorubicin cardiotoxicity.
Does alginate oligosaccharide pretreatment prevent acute doxorubicin cardiotoxicity in mice?
Alginate oligosaccharide is a potent compound that prevents acute doxorubicin cardiotoxicity in a preclinical model by suppressing oxidative stress and ER-mediated apoptosis.
Doxorubicin (DOX) is a highly potent chemotherapeutic agent, but its usage is limited by dose-dependent cardiotoxicity. DOX-induced cardiotoxicity involves increased oxidative stress and activated endoplasmic reticulum-mediated apoptosis. Alginate oligosaccharide (AOS) is a non-immunogenic, non-toxic and biodegradable polymer, with anti-oxidative, anti-inflammatory and anti-endoplasmic reticulum stress properties. The present study examined whether AOS pretreatment could protect against acute DOX cardiotoxicity, and the underlying mechanisms focused on oxidative stress and endoplasmic reticulum-mediated apoptosis. We found that AOS pretreatment markedly increased the survival rate of mice insulted with DOX, improved DOX-induced cardiac dysfunction and attenuated DOX-induced myocardial apoptosis. AOS pretreatment mitigated DOX-induced cardiac oxidative stress, as shown by the decreased expressions of gp91 (phox) and 4-hydroxynonenal (4-HNE). Moreover, AOS pretreatment significantly decreased the expression of Caspase-12, C/EBP homologous protein (CHOP) (markers for endoplasmic reticulum-mediated apoptosis) and Bax (a downstream molecule of CHOP), while up-regulating the expression of anti-apoptotic protein Bcl-2. Taken together, these findings identify AOS as a potent compound that prevents acute DOX cardiotoxicity, at least in part, by suppression of oxidative stress and endoplasmic reticulum-mediated apoptosis.
Guo et al. (Tue,) conducted a other in Acute doxorubicin cardiotoxicity. Alginate oligosaccharide (AOS) pretreatment vs. Doxorubicin without AOS pretreatment was evaluated on Survival rate, cardiac dysfunction, and myocardial apoptosis. Alginate oligosaccharide pretreatment increased survival, improved cardiac dysfunction, and attenuated myocardial apoptosis in mice with acute doxorubicin cardiotoxicity.