Selenomethionine Alleviates DON-Induced Oxidative Stress via Modulating Keap1/Nrf2 Signaling in the Small Intestinal Epithelium.
J Agric Food Chem
; 71(1): 895-904, 2023 Jan 11.
Article
em En
| MEDLINE
| ID: mdl-36535023
ABSTRACT
The small intestinal epithelium is regulated in response to various beneficial or harmful environmental information. Deoxynivalenol (DON), a mycotoxin widely distributed in cereal-based feeds, induces oxidative stress damage in the intestine due to the mitochondrial stress. As a functional nutrient, selenomethionine (Se-Met) is involved in synthesizing several antioxidant enzymes, yet whether it can replenish the intestinal epithelium upon DON exposure remains unknown. Therefore, the in vivo model C57BL/6 mice and the in vitro model MODE-K cells were treated with l-Se-Met and DON alone or in combination to confirm the status of intestinal stem cell (ISC)-driven epithelial regeneration. The results showed that 0.1 mg/kg body weight (BW) Se-Met reinstated the growth performance and integrity of jejunal structure and barrier function in DON-challenged mice. Moreover, Lgr5+ ISCs and PCNA+ mitotic cells in crypts were prominently increased by Se-Met in the presence of DON, concomitant with a significant increase in absorptive cells, goblet cells, and Paneth cells. Simultaneously, crypt-derived jejunal organoids from the Se-Met + DON group exhibited more significant growth advantages ex vivo. Furthermore, Se-Met-stimulated Keap1/Nrf2-dependent antioxidant system (T-AOC and GSH-Px) to inhibit the accumulation of ROS and MDA in the jejunum and serum. Moreover, Se-Met failed to rescue the DON-triggered impairment of cell antioxidant function after Nrf2 perturbation using its specific inhibitor ML385 in MODE-K cells. In conclusion, Se-Met protects ISC-driven intestinal epithelial integrity against DON-induced oxidative stress damage by modulating Keap1/Nrf2 signaling.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Selenometionina
/
Tricotecenos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Agric Food Chem
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China