Function of capric acid in cyclophosphamide-induced intestinal inflammation, oxidative stress, and barrier function in pigs

Sang In Lee,Kyung Soo Kang

doi:10.1038/s41598-017-16561-5

Abstract

The small intestine is not only critical for nutrient absorption, but also serves as an important immune organ. Medium-chain fatty acids have nutritional and metabolic effects and support the integrity of the intestinal epithelium. However, their roles in intestinal immunity in pigs are not fully understood. We investigated the effects of a medium-chain fatty acid, capric acid, on intestinal oxidative stress, inflammation, and barrier function in porcine epithelial cells and miniature pigs after treatment with the immune suppressant cyclophosphamide. Capric acid alleviated inflammatory cytokine production (TNF-α and IL-6) and related gene expression (NF-κB, TNF-α, IFN-γ), alleviated oxidative stress (GSSG/GSH ratio, H2O2, and malondialdehyde), and increased oxidative stress-related gene expression (SOD1 and GCLC) in cyclophosphamide-treated IPEC-J2 cells. The permeability of FD-4 and expression of ZO-1 and OCLN in cyclophosphamide-treated IPEC-J2 cells were reduced by capric acid. Dietary capric acid reduced TNF-α, IL-6, and MDA levels and increased SOD, GPx, and the expression of genes related to pro-inflammatory, oxidative stress, and intestinal barrier functions in cyclophosphamide-treated miniature pigs. These results revealed that capric acid has protective effects against cyclophosphamide-induced small intestinal dysfunction in pigs.

Highlights

The gastrointestinal (GI) tract is important for the digestion, absorption, and metabolism of nutrients, and serves as a critical immune organ, since it has the most immune cells in the body[1]
We found that capric acid, an Medium-chain fatty acids (MCFAs), significantly reduced the tumour necrosis factor (TNF)-α and IL-6 concentrations after cyclophosphamide treatment in porcine intestinal epithelial cells
The authors elucidated the mechanism by which capric acid attenuates cytokine production and reported that capric acid at 100 mM significantly suppresses phosphorylated MAPKs, such as p38, JNK, and ERK, and significantly increased NF-kB p65 translocation[24]

Summary

Introduction

The gastrointestinal (GI) tract is important for the digestion, absorption, and metabolism of nutrients, and serves as a critical immune organ, since it has the most immune cells in the body[1]. The intestinal barrier is composed of a single layer of columnar epithelial cells sealed by junctional complexes including, tight and adherens junctions, in close proximity to the apical and lateral side of the paracellular space. These structures are affected by oxidative stress, since the pathophysiology of a redox imbalance is characterised by disrupted junctional complexes[13,14,15]. We investigated the functions of capric acid in small intestinal epithelial cells after cyclophosphamide treatment in pigs. This is the first study of the effect of capric acid on intestinal oxidative stress, inflammation, and barrier function in porcine epithelial cells and miniature pigs

Methods

Results

Conclusion