Research Express@NCKU - Articles Digest

Sepsis is characterized by a systemic inflammatory response to bacterial infection, especially Gram-negative bacteria. Sepsis is part of a spectrum of conditions ranging from the systemic inflammatory response syndrome (SIRS) to septic shock and multiple organ dysfunction syndrome (MODS). It is estimated that more than 215,000 patients die of sepsis in the U.S. every year. Despite significant advances in managing sepsis, it continues to be the main cause of mortality in intensive care units. The mortality associated with sepsis ranges from around 26% for SIRS to around 82% for septic shock.

Oxidative stress is defined as an increase in reactive oxygen species and a decrease in circulating antioxidants. Oxidative stress has been reported to be involved in the pathogenesis of sepsis. During sepsis, macrophages are activated by endotoxin and/or pro-inflammatory cytokines. This activation initiates an expression of NADPH oxidase and inducible nitric oxide synthase (iNOS), and generates superoxide anion and nitric oxide, respectively. In the physiological condition, superoxide anion is transformed to hydrogen peroxide by the action of superoxide dismutase. Subsequently, hydrogen peroxide will be metabolized to water by glutathione peroxidase and catalase. However, once the reactive oxygen species are extremely increased, this endogenous metabolism will be damaged. Superoxide will act with nitric oxide to form peroxynitrite and hydroxyl radical. Both hydroxyl radical and peroxynitrite play the crucial roles in oxidative stress and hepatic failure during sepsis.

We have found that one single dose of sesame oil has significant protection against sepsis. Sesame oil attenuates multiple organ failure and decreases mortality no matter it is given before or after the onset of sepsis; however, the effective component in it has not been clarified. According to British Standard Institute report in 2000, the main components of sesame oil are fatty acids, and less than 2% of lignans and -tocopheral, both of which are potent antioxidants. However, neither fatty acids nor -tocopherol is involved in the protection against sepsis by sesame oil. Among the lignans, sesamol is the main anti-oxidative component in sesame oil. Sesamol is reported to decrease free radical generation and lipid peroxidation. In addition, to manage the critical situation in endotoxemia, sesamol might be more beneficial than sesame oil. First, water-soluble sesamol can easily be prepared and administered to mitigate liver-damaging oxidative stress. Second, during sepsis, impaired gastric mucosa and acid secretion may decrease the digestion and absorption of drugs. However, the effect of sesamol on sepsis has never been investigated.

After sepsis is induced by cecal ligation and puncture, sesamol is administered every 6 h. The survival rate is determined within 48 h. Hepatic dysfunction, oxidative stress, nitric oxide, and iNOS expression were assessed 12 h after cecal ligation and puncture. Sesamol delays mortality and attenuates hepatic injury in septic rats. Hepatic lipid peroxidation, hydroxyl radical, and superoxide anion levels are significantly lower in sesamol-treated septic rats. Furthermore, sesamol inhibited hepatic nitrite production and the iNOS expression in septic rats. We hypothesize that sesamol inhibits the production of nitric oxide, thereby attenuates lipid peroxidation-associated hepatic injury and delays mortality in septic rats. Additionally, although one or more components of sesame oil may contribute to the anti-oxidative effect, it is likely that sesamol is the important component that accounts for sesame oil’s protective effect against sepsis in rats.

Effect of sesamol (SM) on survival rate of rats with cecal ligation and puncture (CLP)-induced sepsis. Rats were divided into two groups: CLP group rats were given only CLP; and CSM group rats were given sesamol every 6 h after CLP. Survival rate was recorded for 48 h after CLP (n = 14) (Log-rank test).