chrysin and Sepsis

The incidence of myocardial dysfunction caused by sepsis is high, and the mortality of patients with sepsis can be significantly increased. During sepsis, oxidative stress and inflammation can lead to severe organ dysfunction. Flavone chrysin is one of the indispensable biological active ingredients for different fruits and vegetables and has antioxidant and anti-inflammatory properties. However, it is not clear whether chrysin is an effective treatment for heart dysfunction caused by sepsis. We found that it had protective effects against the harmful effects caused by LPS, manifested in improved survival, normalized cardiac function, improved partial pathological scores of myocardial tissue, and remission of apoptosis, as well as reduced oxidative stress and inflammation. Mechanism studies have found that chrysin is an important antioxidant protein, a key regulator of heme oxygenase 1 (HO-1). We found that HO-1 levels were increased after LPS intervention, and chrysin further increased HO-1 levels, along with the addition of Nrf2, a regulator of antioxidant proteins. Pretreatment with PD98059, an extracellular signal-regulated kinase-specific inhibitor, blocked chrysin-mediated phosphorylation of Nrf2 and the nuclear translocation of Nrf2. The protective effect of chrysin on sepsis-induced cardiac dysfunction was blocked by ZnPP, which is a HO-1 blocker. Chrysin increased antioxidant activity and reduced markers of oxidative stress (SOD and MDA) and inflammation (MPO and IL-1β), all of which were blocked by ZnPP. This indicates that HO-1 is the upstream molecule regulating the protective effect of chrysin. Thus, by upregulation of HO-1, chrysin protects against LPS-induced cardiac dysfunction and inflammation by inhibiting oxidative stress.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cell Line; Disease Models, Animal; Flavonoids; Heart Diseases; Heme Oxygenase-1; Inflammation Mediators; Lipopolysaccharides; Male; Membrane Proteins; Mice, Inbred C57BL; Myocytes, Cardiac; NF-E2-Related Factor 2; Oxidative Stress; Rats; Sepsis; Signal Transduction; Ventricular Function, Left

Chrysin (CR) is a flavone found in propolis and many plants. Lipopolysaccharide (LPS) is a component of the cell wall of gram-negative bacteria that causes sepsis. The purpose of this study was to investigate the effects of CR on LPS-induced sepsis in rats. LPS intraperitoneal and a single dose and CR were given orally for 10 days. Rats were sacrificed, blood samples were taken, liver, lung, and kidney tissues were dissected, homogenized, and histopathological analysis was carried out. When CR groups compared to sepsis group, CR significantly decreased the serum levels of aspartate transaminase (AST) and alanine aminotransferase (ALT), interleukin-1 beta (IL-1β), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and levels of malondialdehyde (MDA) in tissues. CR also increased the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in tissues. Histopathological findings were consistent with biochemical findings. Conclusion, CR could reduce the oxidative stress markers and cytokines in sepsis. PRACTICAL APPLICATIONS: Our approach is to determine the antioxidant and anti-inflammatory effects of chrysin, known as a flavolonoid, which are found in many plants and foods such as honey and propolis. In this study, experimental sepsis model was created using LPS. According to the results of the study, CR can attribute to the ameliorating of oxidative damage in tissues (lung, liver, and kidney) and it can suppress the sepsis-associated acute tissue injury via reduction of inflammation in rats. Even, CR can be used as a pharmacological agent in inflammatory diseases caused by other sources and in many cases causing oxidation.

Topics: Animals; Flavonoids; Lipopolysaccharides; Oxidative Stress; Rats; Sepsis

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Aspartate Aminotransferases; Biomarkers; Colony Count, Microbial; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Flavonoids; Gene Expression; Kaempferols; Leukocyte Count; Liver; Male; Mice; Mice, Inbred ICR; Nitric Oxide; Peroxidase; Sepsis; Survival Analysis; Tumor Necrosis Factor-alpha