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Ammonia is an important component of PM2.5 and PM10, and is also a major harmful gas in intensive and large-scale pig houses, which poses a potential threat to the health of farmers and animals. Intestinal tract is the largest immune organ in the body and is also an important target organ for ammonia exposure. However, the potential toxicity mechanism of ammonia exposure to the intestine remains unclear. L-selenomethionine is an important source of organic selenium with the advantages of high bioavailability, safety and high efficiency. In order to explore the mechanism of ammonia enterotoxicity and the mitigation effect of L-selenomethionine on ammonia enterotoxicity, multi-dimensional ammonia toxicity models and L-selenomethionine intervention models were established in vivo and in vitro. The results showed that ammonia exposure up-regulated the levels of iron, ROS, MDA, and LPO in the small intestinal tissue and the IPEC-J2 cell, down-regulated the activities of antioxidant enzymes and the content of GSH, inhibited the Nrf2 pathway, significantly altered the expression of ferroptosis (TFR-1, FPN-1, FTH1, SLC7A11, GPX4, ACSL4) and intestine tight junctions (Claudin-1, Occludin, ZO-1) genes. Compared with the ammonia exposure group, L-selenomethionine group could significantly improve the changes of these ferroptosis indicators by affecting ROS and iron levels through Nrf2 pathway. Our results indicated that L-selenomethionine inhibited small intestinal epithelial cells ferroptosis caused by ammonia exposure through regulating ROS-mediated iron metabolism. [Display omitted] ● Ammonia exposure caused intestinal ferroptosis. ● Excessive ROS accumulation-mediated ferroptosis targeted intestinal damage. ● The bioactivity of L-selenomethionine was evaluated in multiple dimensions. ● L-selenomethionine reduces ammonia toxicity by Nrf2 pathway/ferroptosis axis. [ABSTRACT FROM AUTHOR]

Ammonia has been reported to have a variety of toxicity to aquatic animals, farm animals and humans. However, its potential toxicity on the intestines remains unknown. L -selenomethionine is one of the important organic selenium sources. However, the mitigating effect of L -selenomethionine on ammonia exposure toxicity is still lacking. Therefore, in this study, the mechanism of toxic action of ammonia on intestinal tract and the detoxification effect of L -selenomethionine were examined. We evaluated the intestinal toxicity of ammonia and the alleviating effect of L -selenomethionine in an in vivo model, and then verified it in vitro model by a variety of cutting-edge experimental techniques. Our results showed that ammonia exposure causes oxidative stress, necroptosis, Th1/Th2 imbalance and inflammation in the intestinal tissue and the intestinal cells, and L -selenomethionine had a significant mitigation effect on the changes of these indexes induced by ammonia. In conclusion, ammonia exposure caused oxidative stress and Th1/Th2 imbalance in the porcine small intestine and IPEC-J2 cells, and that excessive ROS accumulation-mediated necroptosis targeted inflammatory responses, resulting in the destruction of tight connections of intestinal cells, thereby causing intestinal barrier dysfunction. L -selenomethionine could effectively reduce the intestinal injury caused by ammonia exposure and antagonize the toxic effect of ammonia. [Display omitted] • Ammonia is a toxic pollutant, which has a strong toxic effect on intestinal tract. • Ammonia exposure causes oxidative stress and Th1/Th2 imbalance in intestinal cells. • Excessive ROS accumulation-mediated necroptosis targeted inflammatory responses. • L -selenomethionine can mitigate the toxic effect of ammonia on intestinal tract. [ABSTRACT FROM AUTHOR]

Ammonia (NH 3) is a common air pollutant, which poses a serious threat to farm animals. L-selenomethionine is organic selenium (Se), which can inhibit intracellular ROS generation, block ROS-dependent autophagy, promote mitochondrial energy metabolism, and enhance the body's immunity. Lung, as an important organ of the respiratory system, is highly susceptible to the toxic effects of NH 3. However, there were few studies on the mechanism of toxic effects of NH 3 on lung tissues. The aim of this study was to investigate the effect of NH 3 on the lungs in pigs and the alleviating effect of L-selenomethionine. Twenty-four Large White*Duroc*Min pigs were randomly assigned to 4 groups: control group, NH 3 group, Se group, and NH 3 +Se group. The results showed that exposure to NH 3 caused damage and inflammation in lung tissues and significantly increased blood NH 3 concentration. NH 3 induced changes of oxidative stress indexes (GSH, GSH-Px, SOD, MDA, Keap1, Nrf2, and HO-1) and expressions of energy metabolism related genes (HK1, HK2, PFK, PK, LDHA, and HIF-1α). Ultrastructure showed that mitochondrial damage and autophagosome increased significantly, and the expression levels of autophagy related genes (Beclin1, ATG5, ATG7, ATG10, and p62) changed. However, the addition of L -selenomethionine alleviated the above changes, but there was still a significant difference compared with the control group (P < 0.05). This finding can provide a new evidence for mitigation of NH 3 toxicity. [Display omitted] • Ammonia is a typical air pollutant, which has a strong toxic effect on respiratory system. • Ammonia exposure causes lung damage by oxidative stress and energy metabolism disorder. • ROS-mediated excessive autophagy is important mechanisms of ammonia toxicity. • L -selenomethionine can mitigate the toxic effect of ammonia exposure on lungs. [ABSTRACT FROM AUTHOR]

Ammonia (NH 3) is a hazardous substance to human and animal health. Selenium (Se) is an essential micronutrient with multiple health benefits. The present study aimed to verify whether and how Se supplementation has a protective role against NH 3 mediated-nephrotoxicity in pigs. A Se-NH 3 interaction model was established in pigs and the kidney samples were collected after a 30-day treatment period. The results showed that NH 3 exposure inhibited the PI3K/AKT/mTOR pathway and enhanced the secretion of inflammatory cytokines to induce autophagy and inflammation. Se can regulate the PI3K/AKT/mTOR pathway and attenuate the secretion of inflammatory cytokines altered by NH 3 to reduce autophagy and inflammation. In addition, Se co-treatment inhibited ROS production, elevated the activities of antioxidant systems, and increased the expression of 13 selenoproteins in pig kidneys caused by NH 3 exposure. These results implied that L -selenomethionine can moderate NH 3 -induced nephrotoxicity in pigs. Our study gives new ideas for the specific mechanism of NH 3 nephrotoxicity and provides a reference for comparative medicine and clinical medication. [Display omitted] • Excess NH 3 induced inflammatory damage in pig kidneys. • NH 3 led to autophagy through inhibition of PI3K/AKT/mTOR pathway. • 0.50 mg/kg of Se showed a nephroprotective effect against NH 3. • Selenoproteins contributed to the detoxification of NH 3 by Se. [ABSTRACT FROM AUTHOR]

Ammonia (NH 3) is a major pollutant in livestock houses and atmospheric environment. It has been demonstrated that NH 3 can cause a series of damage to animals and human. However, toxicity evaluation of NH 3 on farm animals was rarely reported, especially in the intestinal microflora. Therefore, in this study, twenty-four 125-day-old fattening pigs were randomly divided into 4 groups: control group, NH 3 group (88.2 mg m−3 < NH 3 concentration < 90.4 mg m−3), Se group (Se content: 0.5 mg kg−1), and NH 3 + Se group (88.2 mg m−3 < NH 3 concentration < 90.4 mg m−3, Se content: 0.5 mg kg−1), and the effects of NH 3 and L -Selenomethionine on the microbiota composition in the jejunum and the levels of inflammatory markers in feces of fattening pigs were examined by 16S rDNA and ELISA, respectively. Our results showed that the content of Matrix metalloproteinase-9 (MMP-9), Myeloperoxidase (MPO), Lactoferrin (LTF) and Calprotectin in the ammonia group (A group) were significantly elevated compared to the control group, and the content of MMP-9, MPO, LTF and Calprotectin in the A + Se group were significantly reduced. A significant difference in microbiota composition in the phylum, class, family and genus levels was found in the A group and the NH 3 + Se group. There was a negative correlation between Streptococcus and Calprotectin. Our results indicated that excessive NH 3 inhalation could cause changes in inflammatory markers and beta diversity of intestinal microflora in fattening pigs. We found there was a positive correlation between MPO and Pseudomonas. In addition, we first proposed that L -Selenomethionine could improve the imbalance of microbial flora and the inflammatory injury caused by NH 3. Changes in intestinal microflora and inflammatory markers can be used as important indicators to evaluate NH 3 toxicity, and studying changes in intestinal microflora is also an important mechanism to reveal NH 3 toxicity. ga1 • Ammonia is a typical pollutant in atmospheric environment and livestock production. • Excessive ammonia exposure can cause the changes in inflammatory markers. • Excessive ammonia exposure can cause the imbalance of intestinal microflora. • L -selenomethionine can improve the imbalance of intestinal flora caused by ammonia. • Intestinal flora is involved in the toxic mechanism of ammonia. [ABSTRACT FROM AUTHOR]