Gossypol improves myocardial dysfunction caused by sepsis by regulating histone acetylation

Abstract

Gossypol is a polyphenol from the cotton plant with anti-inflammatory and anti-oxidation activities and can also function as a histone deacetylase (HDAC) inhibitor. Sepsis is an inflammatory disease with high mortality. Inflammation, oxidative stress, and epigenetic factors are involved in sepsis and its complications. The biological activities of gossypol strongly suggest the potential effects of gossypol on sepsis. In the present study, the beneficial effects of gossypol on sepsis were evaluated. We established a cecal ligation and puncture (CLP) mouse model of sepsis and treated CLP mice with gossypol. The survival rate, serum level of myocardial injury markers, and myocardial level of oxidation markers were measured. We also administered gossypol to lipopolysaccharide (LPS)-treated primary cardiomyocytes. The production of pro-inflammatory cytokines, activation of protein kinase B (AKT) and IκB kinase (IKK), acetylation of histone, and expression of HDACs were measured. Gossypol prevented the death of CLP mice and ameliorated myocardial damage in CLP mice. Moreover, gossypol decreased oxidative factors, while promoting antioxidant production in CLP mice. Gossypol prevented LPS and cytosine-phosphate-guanosine-induced expression of pro-inflammatory cytokines, suppressed LPS-induced activation of AKT and IKK, inhibited histone acetylation, and decreased the expression of HDACs. In conclusion, gossypol ameliorates myocardial dysfunction in mice with sepsis.