Liu Yongshi, Lv Xi, Yuan Heling, Wang Xiaoming, Huang Jinhu, Wang Liping
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
Toxics. 2024 Sep 30;12(10):719. doi: 10.3390/toxics12100719.
Oxidative stress frequently contributes to intestinal barrier injury in animals and humans. It was reported that both Selenomethionine (SeMet) and allicin exhibit protective effects against a range of diseases caused by oxidative stress. This study aimed to investigate the synergistic antioxidant effects and underlying mechanisms of SeMet and allicin on a HO-induced intestinal barrier injury model using IPEC-J2 cells and mice. The results showed that HO induced severe oxidative stress, including a decrease in cell viability, antioxidant level, migration capacity, and cell integrity. SeMet and allicin exhibited significant synergistic anti-oxidative effects on intestinal epithelial cells. The combined use of SeMet and allicin increased SOD activity, GSH content, and GSH/GSSG ratio while decreasing MDA, NO, and ROS content levels. Furthermore, we found that SeMet and allicin synergistically activated the nuclear factor erythroid-related factor 2 (Nrf2)-NAD(P)H dehydrogenase [quinone] 1 (NQO1) signaling pathway and down-regulated endoplasmic reticulum stress (ER stress)-related proteins. However, the synergistic antioxidative and intestinal barrier protective effects of SeMet and allicin were abolished by Nrf2 inhibitor ML385 in vitro and in vivo. In conclusion, SeMet and allicin synergistically attenuate intestinal barrier injury induced by excessively oxidative stress through the activation of the Nrf2 signaling pathway and inhibition ER stress. These findings support that the combined use of SeMet and allicin could enhance antioxidative properties and alleviate intestinal injury in further clinical practice.
氧化应激常常导致动物和人类的肠道屏障损伤。据报道，硒代蛋氨酸（SeMet）和大蒜素均对由氧化应激引起的一系列疾病具有保护作用。本研究旨在利用IPEC-J2细胞和小鼠，研究SeMet和大蒜素对过氧化氢（HO）诱导的肠道屏障损伤模型的协同抗氧化作用及其潜在机制。结果表明，HO诱导了严重的氧化应激，包括细胞活力、抗氧化水平、迁移能力和细胞完整性的降低。SeMet和大蒜素对肠上皮细胞表现出显著的协同抗氧化作用。SeMet和大蒜素联合使用可提高超氧化物歧化酶（SOD）活性、谷胱甘肽（GSH）含量以及GSH/氧化型谷胱甘肽（GSSG）比值，同时降低丙二醛（MDA）、一氧化氮（NO）和活性氧（ROS）含量水平。此外，我们发现SeMet和大蒜素协同激活核因子红细胞相关因子2（Nrf2）-烟酰胺腺嘌呤二核苷酸磷酸（NAD(P)H）脱氢酶[醌]1（NQO1）信号通路，并下调内质网应激（ER应激）相关蛋白。然而，Nrf2抑制剂ML385在体外和体内均消除了SeMet和大蒜素的协同抗氧化和肠道屏障保护作用。总之，SeMet和大蒜素通过激活Nrf2信号通路和抑制ER应激，协同减轻过度氧化应激诱导的肠道屏障损伤。这些发现支持在进一步的临床实践中，SeMet和大蒜素联合使用可增强抗氧化性能并减轻肠道损伤。
