Sodium Butyrate Ameliorates Oxidative Stress-Induced Intestinal Epithelium Barrier Injury and Mitochondrial Damage through AMPK-Mitophagy Pathway

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.

Neuroprotective Effects of Sodium Butyrate and Monomethyl Fumarate Treatment through GPR109A Modulation and Intestinal Barrier Restoration on PD Mice

“…Additionally, as we have depicted above, mitochondrial dysfunction in the brain is prone to result in neurodegeneration. According to certain reports, butyrate can regulate mitochondrial dysfunction and lessen oxidative stress [ 41 , 42 , 43 ]. Li et al reported that butyrate can reduce oxidative stress-induced intestinal epithelium barrier injury and mitochondrial damage through the AMPK-mitophagy pathway [ 42 ], suggesting a possible mechanism by which NaB could exert its neuroprotective effects via improved mitochondrial function.…”

Protection by -Biotics against Hypertension Programmed by Maternal High Fructose Diet: Rectification of Dysregulated Expression of Short-Chain Fatty Acid Receptors in the Hypothalamic Paraventricular Nucleus of Adult Offspring

“…In this regard, butyrate activates nuclear transcription factors, such as peroxisome proliferator-activated receptor γ [ 67 ], to antagonize nuclear factor-κB signal transduction and exert an anti-inflammatory effect in the gut. It also activates the ATP-activated protein kinase signaling pathway to alleviate oxidative stress-induced intestinal epithelium barrier injury [ 68 ].…”

Protective Effect of Phloretin against Hydrogen Peroxide-Induced Oxidative Damage by Enhancing Autophagic Flux in DF-1 Cells

“…The role of autophagy in oxidative stress injury is still controversial. Autophagy has been reported to play a positive effect in promoting cell survival and antiapoptosis under H 2 O 2 -induced oxidative stress [40,41]. However, other studies have shown that H 2 O 2 induces cytotoxicity by triggering autophagy [42,43].…”