astaxanthine and Heart-Diseases

Cardiac dysfunction is a significant manifestation of sepsis and it is associated with the prognosis of the disease. Astaxanthin (ATX) has been discovered to serve a variety of pharmacological effects, including anti‑inflammatory, antioxidant and antiapoptotic properties. The present study aimed to investigate the role and mechanisms of ATX in sepsis‑induced myocardial injury. Male C57BL/6 mice were divided into three groups (15 mice per group): Control group, lipopolysaccharide (LPS) group and LPS + ATX group. The cardiac dysfunction model was induced through an intraperitoneal injection of LPS (10 mg/kg) and ATX (40 mg/kg) was administered to the LPS + ATX group by intraperitoneal injection 30 min following the administration of LPS. All animals were sacrificed after 24 h. Inflammatory cytokine levels in the serum were detected using ELISAs, and cardiac B‑type natriuretic peptide (BNP) levels were analyzed using western blot analysis and reverse transcription‑quantitative PCR. Furthermore, the extent of myocardial injury was evaluated using pathological analysis, and cardiomyocyte apoptosis was analyzed using a TUNEL assay, in addition to determining the expression levels of Bcl‑2 and Bax. The expression levels of proteins involved in the mitogen activated protein kinase (MAPK) and PI3K/AKT signaling pathways were also analyzed using western blot analysis. ATX significantly suppressed the LPS‑induced increased production of TNF‑α and IL‑6 and suppressed the protein expression levels of BNP, Bax and Bcl‑2 to normal levels. ATX also prevented the histopathological changes to the myocardial tissue and reduced the extent of necrosis. Furthermore, the treatment with ATX suppressed the LPS‑activated MAPK and PI3K/AKT signaling. ATX additionally exerted a protective effect on cardiac dysfunction caused by sepsis by inhibiting MAPK and PI3K/AKT signaling.

Topics: Animals; Anti-Inflammatory Agents; Disease Models, Animal; Gene Expression Regulation; Glycogen Synthase Kinase 3 beta; Heart Diseases; Injections, Intraperitoneal; Lipopolysaccharides; Male; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Sepsis; TOR Serine-Threonine Kinases; Treatment Outcome; Xanthophylls

Myocardial fibrosis contributes to cardiac dysfunction. Astaxanthin (AST), a member of the carotenoid family, is a well-known antioxidant, but its effect on and underlying mechanisms in myocardial fibrosis are poorly understood.. In vivo, myocardial fibrosis and cardiac dysfunction were induced using transverse aortic constriction (TAC). AST was administered to mice for 12weeks post-surgery. In vitro, transforming growth factor β1 (TGF-β1) was used to stimulate human cardiac fibroblasts (HCFs). EX-527 (6-chloro-2, 3, 4, 9-tetrahydro-1H-carbazole-1-carboxamide) and SIRT1 siRNA were used to inhibit SIRT1 in vivo and in vitro, respectively. The effects of AST on cardiac function and fibrosis were determined. SIRT1 expression and activity were measured to explore the mechanisms underlying its effects.. AST improved cardiac function and attenuated fibrosis. Receptor activated-SMADs (R-SMADs), including SMAD2 and SMAD3, played important roles in these processes. The TAC surgery-induced increases in the expression of phosphorylated and acetylated R-SMADs were attenuated by treatment with AST, the translocation and transcriptional activity of R-SMADs were also restrained. These effects were accompanied by an increase in the expression and activity of SIRT1. Inhibiting SIRT1 attenuated the acetylation and transcriptional activity of R-SMADs, but not their phosphorylation and translocation.. Our data demonstrate that AST improves cardiac function and attenuates fibrosis by decreasing phosphorylation and deacetylation of R-SMADs. SIRT1 contributes to AST's protective function by reducing acetylation of R-SMADs.. These data suggest that AST may be useful as a preventive/therapeutic agent for cardiac dysfunction and myocardial fibrosis.

Topics: Acetylation; Animals; Fibrosis; Heart Diseases; Humans; Male; Mice; Mice, Inbred C57BL; Myocardium; Phosphorylation; Pressure; Sirtuin 1; Smad2 Protein; Smad3 Protein; Xanthophylls