Abstract
The major end-products of dietary fiber fermentation by 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 at different tissue sites. Several studies showed the inhibitory effects of sodium propionate (SP) on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. We carried out an in vitro model of inflammation on the J774-A1 cell line, by stimulation with lipopolysaccharide (LPS) and H2O2, followed by the pre-treatment with SP at 0.1, 1 mM and 10 mM. To evaluate the effect on acute inflammation and superoxide anion-induced pain, we performed a model of carrageenan (CAR)-induced rat paw inflammation and intraplantar injection of KO2 where rats received SP orally (10, 30, and 100 mg/kg). SP decreased in concentration-dependent-manner the expression of cicloxigenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) following LPS stimulation. SP was able to enhance anti-oxidant enzyme production such as manganese superoxide dismutase (MnSOD) and heme oxygenase-1 (HO-1) following H2O2 stimulation. In in vivo models, SP (30 and 100 mg/kg) reduced paw inflammation and tissue damage after CAR and KO2 injection. Our results 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.
Highlights
The Short-chain fatty acids (SCFAs) are carboxylic acids defined by the presence of an aliphatic tail of two to six carbons
Basal levels of inducible nitric oxide synthase (iNOS) were observed in the control groups, whereas LPS stimulation induced a significant increase in iNOS expression
It was shown that sodium propionate (SP) exerts beneficial effects on the intestinal epithelium, inhibiting inflammation and modulating oxidative stress in a dextran sulfate sodium (DSS)-induced colitis mouse model [2]
Summary
The Short-chain fatty acids (SCFAs) are carboxylic acids defined by the presence of an aliphatic tail of two to six carbons. In the intestine, SCFAs exert a trophic effect on the intestinal epithelium and play a key role in the modulation of colonic blood flow, gastrointestinal (GI) motility, and fluid and electrolyte absorption [3]. Several studies focused their attention on the effect of SCFAs on inflammatory signaling pathways, and it was well demonstrated that butyrate inhibits nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) translocation, cytokines production and prevents oxidative damage in a murine model of nephropathy and colitis [4,5,6]. M1woAirt)he. oMSvPoesrrhe, oowvweeerda, swasneesianssecsrdeesatssheededvtphireaoblviiiflaeitbryailtiiftooynllffooowllllooiwnwgiinnLggPLLSPPSsSt-siinmtidmuuulcaleatdtiioocnyn.t.oTTtohhxeeicJJi77t7y744(-FA-Aig1u1crecelel1slBlsp).rper-etr-etareteadted with SP showed an increased proliferation following LPS-induced cytotoxicity (Figure 1B)
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