Weaning disrupts intestinal antioxidant status, impairs intestinal barrier and mitochondrial function, and triggers mitophagy in piglets1

Abstract

In the present study, we investigated the influence of weaning on antioxidant status, intestinal integrity, mitochondrial function, and the mitophagy level in piglets (weaned at 21 d) during the 1 wk after weaning. The redox status was measured by antioxidant enzymes activities, related genes expression, and malondialdehyde (MDA) content in jejunum. The intestinal barrier function was assessed by the Ussing chamber and expression of tight junction proteins in the jejunum. The function of intestine mitochondria was measured by mitochondrial DNA (mtDNA) content and activities of mitochondria oxidative phosphorylation complexes. The levels of light chain 3-1 (LC3-I), light chain 3-II (LC3-II), PTEN-induced putative kinase 1 (PINK1), and Parkin were determined to investigate whether mitophagy is involved in the weaning process. The results showed that, as compared with the preweaning phase (d 0), weaning suppressed (P < 0.05) the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) on d 3 and d 7 postweaning, decreased (P < 0.05) the expression of copper and zinc superoxide dismutase (Cu/Zn-SOD), manganese-containing superoxide dismutase (Mn-SOD) on d 3 postweaning, declined (P < 0.05) the level of glutathione peroxidase 1 (GPX-1) and glutathione peroxidase 4 (GPX-4) on d 3 and d 7 postweaning, and increased (P < 0.05) MDA content in jejunum on d 3 and d 7 postweaning. The jejunal transepithelial electrical resistance and levels of occludin, claudin-1, and zonula occludens-1 on d 3 and d 7 postweaning were reduced (P < 0.05), and paracellular flux of fluorescein isothiocyanatedextran (4 kDa) on d 3 and d 7 postweaning was increased (P < 0.05). Weaning induced mitochondrial dysfunction, as demonstrated by decreased (P < 0.05) content of mtDNA on d 3 and d 7 postweaning and declined (P < 0.05) activities of mitochondria complexes (I, II, III, IV) in jejunum on d 1, d 3, and d 7 postweaning. Weaning led to an increased (P < 0.05) expression level of mitophagy-related proteins, PINK1 and Parkin, in the intestinal mitochondria, as well as an enhancement (P < 0.05) of the ratio of LC3-II to LC3-I content in the jejunal mucosa on d 1, d 3, and d 7 postweaning. These results suggest that weaning disrupted intestinal oxidative balance, and this imbalance may impair intestinal barrier and mitochondrial function and trigger mitophagy in piglets.

Short-chain fructo-oligosaccharides enhances intestinal barrier function by attenuating mucosa inflammation and altering colonic microbiota composition of weaning piglets

“…The expression of tight junction proteins is important for maintaining the intestinal epithelial barrier (Anderson and Van Itallie 1995). Cao et al (2018) reported that weaning impaired intestinal integrity by down-regulating the expression of ZO1, OCLN and CLDN1 in jejunal mucosa of piglets. In this study, scFOS consumption increased mRNA expression of ZO1, OCLN and CLDN1 in both jejunal and ileal mucosa of weaning piglets, which was consistent with the results of the previous study in neonatal piglets (Le Bourgot et al 2017).…”

Chloroquine Downregulation of Intestinal Autophagy to Alleviate Biological Stress in Early-Weaned Piglets

“…Meanwhile, inflammatory cells release a number of ROS at the site of inflammation, leading to aggravation of oxidative stress, in turn, its product also enhances the pro-inflammatory response [11]. To alleviate the damage caused by oxidative stress, the host forms the first line of the defense system, composed of antioxidant enzymes, such as SOD and GSH-Px, against the deleterious effect of free radicals [5]. Higher antioxidant contents may contribute to beneficial health effects on anti-inflammation and oxidative stress [4].…”

“…Relative protein levels of Beclin1, Sequestosome 1 (P62 /SQSTM1, P62), LC3, and β-actin in the jejunum were determined by Western blotting, as described previously [5]. The primary antibodies used in the present study were as follows: anti-Beclin1 (#3495), anti-P62 (#23214), anti-LC3B, and anti-β-actin (#4970) (Cell Signaling Technology Co., Ltd., Danvers, MA, USA).…”

“…The piglet must adapt abruptly from a liquid milk diet, which is highly digestible and palatable, to a solid dry diet, which is considerably less digestible and palatable. This change results in anatomical and physiological changes to the intestine, thus further affecting intestinal barrier function and absorptive capacity [4,5]. With the disruption of the intestinal barrier, toxins, bacteria, and feed-associated antigens can cross the epithelium, and pro-inflammatory cytokines are activated, then resulting in malabsorption, diarrhea, and poor growth performance [2,6].…”

Nutritional Regulation of Gut Barrier Integrity in Weaning Piglets

“…As mentioned above, weaning impairs intestinal integrity, increases intestinal oxidative stress, and increases the susceptibility of piglets to diseases [83]. The new frontiers used to combat oxidative stress are phytochemical antioxidant compounds in botanical essential oils, i.e., liquid mixtures of volatile compounds obtained from aromatic plants, most commonly by steam distillation.…”