astaxanthine and Sepsis

Astaxanthin, originating from seafood, is a naturally occurring red carotenoid pigment. Previous studies have focused on its antioxidant properties; however, whether astaxanthin possesses a desired anti-inflammatory characteristic to regulate the dendritic cells (DCs) for sepsis therapy remains unknown. Here, we explored the effects of astaxanthin on the immune functions of murine DCs. Our results showed that astaxanthin reduced the expressions of LPS-induced inflammatory cytokines (TNF-α, IL-6, and IL-10) and phenotypic markers (MHCII, CD40, CD80, and CD86) by DCs. Moreover, astaxanthin promoted the endocytosis levels in LPS-treated DCs, and hindered the LPS-induced migration of DCs via downregulating CCR7 expression, and then abrogated allogeneic T cell proliferation. Furthermore, we found that astaxanthin inhibited the immune dysfunction of DCs induced by LPS via the activation of the HO-1/Nrf2 axis. Finally, astaxanthin with oral administration remarkably enhanced the survival rate of LPS-challenged mice. These data showed a new approach of astaxanthin for potential sepsis treatment through avoiding the immune dysfunction of DCs.

Topics: Animals; Anti-Inflammatory Agents; Biomarkers; Cell Movement; Cytokines; Dendritic Cells; Endocytosis; Immunosuppressive Agents; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Sepsis; Xanthophylls

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

Astaxanthin, a xanthophyll carotenoid, holds exceptional promise as an antioxidant, anti-inflammatory, and anticancer agent. No evidence has been published whether it has protective effects on sepsis. The study aimed to investigate the potential effects of astaxanthin on sepsis and multiple organ dysfunctions.. Sepsis was induced by cecal ligation and puncture (CLP) in Sprague-Dawley rats. Animals subjected to CLP and sham-operated control rats were given vehicle or astaxanthin 100 mg/kg/d by oral gavage for 7 d before the operation. The rats were killed at the indicated time points, and the specimen was collected. Cytokines and multiorgan injury-associated enzymatic and oxidative stress indicators were investigated. Multiorgan tissues were assessed histologically, the peritoneal bacterial load and the 72-h survival was observed too.. Sepsis resulted in a significant increase in serum tumor necrosis factor-α, interleukin-1β, and interleukin-6 levels showing systemic inflammatory response; it also caused a remarkable decrease in the superoxide dismutase activity and a significant increase in the malondialdehyde content showing oxidative damage; sepsis caused a great increase in organ injury-associated indicators, including blood urea nitrogen, creatinine, lactate dehydrogenase, creatine kinase isoenzyme-MB isotype, alanine aminotransferase, and aspartate aminotransferase, which was confirmed by histologic examination. And there was a dramatical increase of colony-forming units in the peritoneal cavity in septic rats. Astaxanthin reversed these inflammatory and oxidant response, alleviated the organ injury, reduced the peritoneal bacterial load, and improved the survival of septic rats induced by CLP.. Astaxanthin exerts impressively protective effects on CLP-induced multiple organ injury. It might be used as a potential treatment for clinical sepsis.

Topics: Animals; Creatine Kinase, MB Form; Cytokines; Disease Models, Animal; Male; Multiple Organ Failure; Rats; Rats, Sprague-Dawley; Sepsis; Xanthophylls