作者
Marika Lanza,Giovanna Casili,Alessia Filippone,Michela Campolo,Irene Paterniti,Emanuela Esposito
摘要
The major end‐products of dietary fibre fermentation by the gut microbiota are the short‐chain fatty acids (SCFAs) acetate, propionate and butyrate, which have been shown to modulate host metabolism via effects on metabolic pathways and receptor‐mediated mechanisms at different tissue sites. The beneficial effects of SCFAs on various aspects of gut physiology, barrier function, and metabolism have been well documented. Furthermore, SCFAs can promote intestinal homeostasis and suppress intestinal inflammation. Recently, several reports have been published describing inhibitory effects of SCFA on NF‐κB, one of the key transcription factors regulating genes implicated in innate immunity, cell cycle control, and apoptosis. However, most previous studies mainly focused on butyrate, and few studies have devoted their efforts to other SCFAs such as propionate, although it is abundant as butyrate in the gut and blood. Thus, the purpose of this study is to investigate protective mechanisms of sodium propionate (SP) in inflammatory and oxidative stress responses. The first step was to evaluate the anti‐inflammatory and ant‐oxidant mechanism of SP, by an in vitro model on murine macrophage cell line, J774‐A1, by two different approaches: stimulation with lipopolysaccharide (LPS) from E. coli and H 2 O 2 , both followed by the treatment with SP at different concentrations (0.1–1 and 10 mM ). Moreover, to evaluate the effect on acute inflammation, an in vivo model of Carrageenan (CAR)‐induced rat paw inflammation was performed, where rats were orally treated with different doses of SP (10 mg/kg, 30 mg/kg and 100 mg/kg). Our in vitro results showed that SP (0.1‐1‐10mM) significantly decreased in concentration‐dependent‐manner the expression of pro‐inflammatory mediators, such as cyclooxygenase‐2 (COX‐2) and inducible nitric oxide synthase (iNOS) following LPS stimulation. Moreover, it has been demonstrated that SP (0.1‐1‐10 mM) was able to enhance anti‐oxidant enzyme production such as manganese‐dependent superoxide dismutase (MnSOD) and heme oxygenase‐1 (HO‐1) following H 2 O 2 stimulation. In addition, in in vivo model, SP(30 mg/kg and 100 mg/kg) markedly reduced paw inflammation, thermal hyperalgesia and tissue damage induced by CAR injection. Our results clearly demonstrated the anti‐inflammatory and anti‐oxidant properties of SP, therefore, we propose that SP may be an effective strategy for the treatment of inflammatory diseases. Support or Funding Information No funding This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .