Protective Effects of Ferulic Acid against Heat Stress-Induced Intestinal Epithelial Barrier Dysfunction In Vitro and In Vivo

Abstract

Heat stress is important in the pathogenesis of intestinal epithelial barrier dysfunction. Ferulic acid (FA), a phenolic acid widely found in fruits and vegetables, can scavenge free radicals and activate cell stress responses. This study is aimed at investigating protective effects of FA on heat stress-induced dysfunction of the intestinal epithelial barrier in vitro and in vivo. Intestinal epithelial (IEC-6) cells were pretreated with FA for 4 h and then exposed to heat stress. Heat stress caused decreased transepithelial electrical resistance (TER) and increased permeability to 4-kDa fluorescein isothiocyanate (FITC)-dextran (FD4). Both effects were inhibited by FA in a dose-dependent manner. FA significantly attenuated the decrease in occludin, ZO-1 and E-cadherin expression observed with heat stress. The distortion and redistribution of occludin, ZO-1 and E-cadherin proteins were also effectively prevented by FA pretreatment. Moreover, heat stress diminished electron-dense material detected in tight junctions (TJs), an effect also alleviated by FA in a dose-dependent manner. In an in vivo heat stress model, FA (50 mg/kg) was administered to male Sprague–Dawley rats for 7 consecutive days prior to exposure to heat stress. FA pretreatment significantly attenuated the effects of heat stress on the small intestine, including the increased FD4 permeability, disrupted tight junctions and microvilli structure, and reduced occludin, ZO-1 and E-cadherin expression. Taken together, our results demonstrate that FA pretreatment is potentially protective against heat stress-induced intestinal epithelial barrier dysfunction.

Wnt/β‐catenin‐mediated heat exposure inhibits intestinal epithelial cell proliferation and stem cell expansion through endoplasmic reticulum stress

“…In addition, TJ‐related proteins are involved in the maintenance of paracellular permeability and barrier function, which are necessary for defense against pathogenic bacteria (Bondow, Faber, Wojta, Walker, & Battle, 2012). In vitro and in vivo studies have shown that heat exposure induces disruption of the intestinal integrity (Groschwitz & Hogan, 2009; He et al, 2016), and our results, which showed that heat‐exposure induced a decrease in the TEER values and increases in the FS flux and efflux ratio, were consistent with these previous studies. Likewise, the protein expression of ZO‐1, occludin, and claudin‐1 was significantly reduced in IPEC‐J2 cells exposed to heat for 72 hr.…”

Yeast fermentate prebiotic improves intestinal barrier integrity during heat stress by modulation of the gut microbiota in rats

“…Decreased expression of TJ proteins during heat stress was found in Caco‐2 cells (Gupta et al, ) and in animal studies (Wu et al, ). Inhibition of these proteins expression indicates the disturbance of the TJ barrier functions and accompanied by intestinal permeability (He et al, ). Our results showed that oral administration of S. cerevisiae fermentate to rats before heat stress significantly enhanced TJ proteins expression.…”

“…Decreased expression of TJ proteins during heat stress was found in Caco-2 cells (Gupta et al, 2017) and in animal studies . Inhibition of these proteins expression indicates the disturbance of the TJ barrier functions and accompanied by intestinal permeability (He et al, 2016). Our results showed that oral administration of S. cerevisiae fermentate to rats before heat stress significantly ES-rats were orally gavaged with Saccharomyces cerevisiae fermentate and exposed to heat stress; EC-rats were orally gavaged with Saccharomyces cerevisiae fermentate and kept at room temperature; PS-rats were orally gavaged with PBS and exposed to heat stress; PC-rats were orally gavaged with PBS and kept at room temperature.…”

Ferulic Acid and Naturally Occurring Compounds Bearing a Feruloyl Moiety: A Review on Their Structures, Occurrence, and Potential Health Benefits

“…Fetoni and others () provided functional in vivo evidence that FA limits noise‐induced hearing loss in the guinea‐pig, not only by its radical‐scavenging ability in the peritraumatic period, but also due to the upregulation of the cytoprotective enzyme heme oxygenase‐1 (HO‐1) in guinea‐pig cochleae. Further protective effects of FA have been recently described on kidneys (Alam and others ), the liver (Maruf and others ), intestine (He and others ), and pancreas (Roy and others ), among others.…”