Abstract
Sodium butyrate has gained increasing attention for its vast beneficial effects. However, whether sodium butyrate could alleviate oxidative stress-induced intestinal dysfunction and mitochondrial damage of piglets and its underlying mechanism remains unclear. The present study used a hydrogen peroxide- (H2O2-) induced oxidative stress model to study whether sodium butyrate could alleviate oxidative stress, intestinal epithelium injury, and mitochondrial dysfunction of porcine intestinal epithelial cells (IPEC-J2) in AMPK-mitophagy-dependent pathway. The results indicated that sodium butyrate alleviated the H2O2-induced oxidative stress, decreased the level of reactive oxygen species (ROS), increased mitochondrial membrane potential (MMP), mitochondrial DNA (mtDNA), and mRNA expression of genes related to mitochondrial function, and inhibited the release of mitochondrial cytochrome c (Cyt c). Sodium butyrate reduced the protein expression of recombinant NLR family, pyrin domain-containing protein 3 (NLRP3) and fluorescein isothiocyanate dextran 4 kDa (FD4) permeability and increased transepithelial resistance (TER) and the protein expression of tight junction. Sodium butyrate increased the expression of light-chain-associated protein B (LC3B) and Beclin-1, reduced the expression of P62, and enhanced mitophagy. However, the use of AMPK inhibitor or mitophagy inhibitor weakened the protective effect of sodium butyrate on mitochondrial function and intestinal epithelium barrier function and suppressed the induction effect of sodium butyrate on mitophagy. In addition, we also found that after interference with AMPKα, the protective effect of sodium butyrate on IPEC-J2 cells treated with H2O2 was suppressed, indicating that AMPKα is necessary for sodium butyrate to exert its protective effect. In summary, these results revealed that sodium butyrate induced mitophagy by activating AMPK, thereby alleviating oxidative stress, intestinal epithelium barrier injury, and mitochondrial dysfunction induced by H2O2.
Highlights
The intestinal epithelium barrier is known as the important barrier to prevent the invasion of toxins or antigens [1]
Under laser confocal microscope, we found that compared with the control group, H2O2 reduced the ratio of JC-1 aggregates to monomer (P < 0:05), indicating that the mitochondrial membrane potential was reduced, and the sodium butyrate treatment alleviated the decrease of cell mitochondrial membrane potential induced by H2O2 (P < 0:05) (Figure 2(b))
Compared with the NaB+H2O2 group, Mdivi-1 and Compound C treatments significantly increased the reactive oxygen species (ROS) levels of IPEC-J2 cells (P < 0:05) (Figure 6(e)). These results indicate that inhibition of mitophagy or AMPKα weakens the protective effects of sodium butyrate on mitochondria under oxidative stress
Summary
The intestinal epithelium barrier is known as the important barrier to prevent the invasion of toxins or antigens [1]. Studies have found that oxidative stress is involved in the intestinal barrier impairment of piglets, which mainly refers to the imbalance of reactive oxygen species (ROS) and antioxidant system [2, 3]. The overproduction of ROS can cause lipid peroxidation, protein, and DNA damage [4]. Multiple studies have shown that dietary sodium butyrate can protect the intestinal barrier of piglets by providing energy for intestinal epithelial cells, antiinflammation, histone deacetylation, immune regulation [5,6,7], etc. The in vivo rat experiments and in vitro intestinal epithelial cell experiments have demonstrated that the protective effects of intestinal barrier function by sodium butyrate are related to its antioxidant capacity [8,9,10].
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