Pyrroloquinoline Quinone Alleviates Intestinal Inflammation and Cell Apoptosis via the MKK3/6-P38 Pathway in a Piglet Model

• Published in: International journal of molecular sciences Vol. 25; no. 17; p. 9723
• Main Authors: Huang, Caiyun, Yu, Xuanci, Du, Ziyuan, Zhu, Zhihao, Shi, Chenyu, Li, Ang, Wang, Fenglai
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.09.2024
• Subjects: Apoptosis; Cytochrome; Cytokines; Diarrhea; Dietary supplements; E coli; Edema; Inflammation; intestine; Kinases; Morphology; Peptides; Phosphorylation; Proteins; pyrroloquinoline quinone; Small intestine; Swine; weaned piglets
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25179723

This study investigates the underlying mechanism through which dietary supplementation of pyrroloquinoline quinone disodium (PQQ) alleviates intestinal inflammation and cell apoptosis in piglets challenged with lipopolysaccharide (LPS). Seventy-two barrows were divided into three groups: control (CTRL), LPS challenged (LPS), and LPS challenged with PQQ supplementation (PQQ + LPS). On d 7, 11, and 14, piglets received intraperitoneal injections of LPS or 0.9% of NaCl (80 μg/kg). After a 4 h interval following the final LPS injection on d 14, blood samples were obtained, and all piglets were euthanized for harvesting jejunal samples. The results showed that dietary supplementation of PQQ improved the damage of intestinal morphology, increased the down-regulated tight junction proteins, and reduced the increase of serum diamine oxidase activity, the intestinal fatty acid binding protein, and TNF-α levels in piglets challenged with LPS (p < 0.05). The proteomics analysis revealed a total of 141 differentially expressed proteins (DEPs), consisting of 64 up-regulated DEPs and 77 down-regulated DEPs in the PQQ + LPS group compared to the LPS group. The KEGG pathway analysis indicated enrichment of the tight junction pathway and the apoptosis pathway (p < 0.05). Compared to the LPS group, the piglets in the PQQ + LPS group had increased levels of Bcl-2 protein, reduced positive apoptosis signals, and a decrease in the abundance of MKK 3/6 and p-p38 proteins (p < 0.05). In conclusion, dietary supplementation of PQQ could alleviate jejunal inflammatory damage and cell apoptosis in piglets challenged with LPS through the MKK3/6-p38 signaling pathway.