Pterostilbene Confers Protection against Diquat-Induced Intestinal Damage with Potential Regulation of Redox Status and Ferroptosis in Broiler Chickens

Abstract

Oxidative stress causes damage to macromolecules, including proteins, DNA, and lipid, and has been recognized as a crucial driver of the onset and progression of several intestinal disorders. Pterostilbene, one of the natural antioxidants, has attracted considerable attention owing to its multiple biological activities. In the present study, we established an oxidative stress model in broiler chickens via injection with diquat to investigate whether pterostilbene could attenuate diquat-induced intestinal damage and reveal the underlying mechanisms. We found that diquat-induced decreases in the activities of superoxide dismutase and glutathione peroxidase and the level of reduced glutathione and the increase in hydrogen peroxide content in plasma and jejunum were significantly alleviated by pterostilbene ( P < 0.05 ). Pterostilbene supplementation also decreased intestinal permeability and jejunal apoptosis rate, improved jejunal villus height and the ratio of villus height to crypt depth, and promoted the transcription and translation of jejunal tight junction proteins occludin and zona occludens 1 in diquat-challenged broilers ( P < 0.05 ). Furthermore, pterostilbene reversed diquat-induced mitochondrial injury in the jejunum, as indicated by the decreased reactive oxygen species level and elevated activities of superoxide dismutase 2 and mitochondrial respiratory complexes ( P < 0.05 ). Importantly, administering pterostilbene maintained iron homeostasis, inhibited lipid peroxidation, and regulated the expression of the markers of ferroptosis in the jejunum of diquat-exposed broilers ( P < 0.05 ). The nuclear factor erythroid 2-related factor 2 signaling pathway in the jejunum of diquat-exposed broilers was also activated by pterostilbene ( P < 0.05 ). In conclusion, our study provides evidence that pterostilbene alleviates diquat-induced intestinal mucosa injury and barrier dysfunction by strengthening antioxidant capacity and regulating ferroptosis of broiler chickens.

Dietary pterostilbene exerts potential protective effects by regulating lipid metabolism and enhancing antioxidant capacity on liver in broilers

“…With the prohibition of antibiotics in feed, the continuous stimulation by the stressors related to large‐scale intensive breeding increased the disease susceptibility of broilers, which severely affected the metabolism in broilers, particularly lipid metabolism. As a resveratrol analogue, PT has been confirmed to possess more desirable properties, such as intestinal absorption capacity, hepatic stability, bioavailability and biotoxicity, and exhibits diverse biological activities and therapeutic potentials, which exerts protective effects against exogenous factors via multiple pathways on various species (Chen et al, 2020; Chen et al, 2023; Liu et al, 2021; Zhou et al, 2019). However, there is still a lack of literature addressing the protective role of PT as a feed additive on the disorder of lipid metabolism in poultry to date.…”

“…Our study found that PT exerted protective effects on liver of broilers against oxidative stress by decreasing the content of MDA and increasing the levels of antioxidant enzymes (T‐SOD, CAT, GSH‐Px), while 400 mg/kg PT supplementation was preferable. It has been reported that PT as an antioxidant agent, could directly react with ROS forming stable semiquinone through 4′‐hydroxyl group, to terminate the ROS oxidative chain reaction (Chen et al, 2023). Additionally, like other polyphenols, PT has been shown to exert antioxidant potential by activating the Nrf2 pathway in a variety of species (Chen et al, 2023; Wang, Liu, Liu, et al, 2022; Wang, Liu, Zhou, et al, 2022; Zhang, Chen, Li, et al, 2020).…”

“…It has been reported that PT as an antioxidant agent, could directly react with ROS forming stable semiquinone through 4′‐hydroxyl group, to terminate the ROS oxidative chain reaction (Chen et al, 2023). Additionally, like other polyphenols, PT has been shown to exert antioxidant potential by activating the Nrf2 pathway in a variety of species (Chen et al, 2023; Wang, Liu, Liu, et al, 2022; Wang, Liu, Zhou, et al, 2022; Zhang, Chen, Li, et al, 2020). Nrf2, a redox‐sensitive transcription regulator of the antioxidant response element promoter region, is considered as the most important antioxidant mechanism, which is pointed intricately connected with lipids metabolism (Meng et al, 2018; Zhao et al, 2015).…”

“…In the therapy of reperfusion‐induced ischaemia rats, PT showed the free radical scavenging property by increasing the activities of CAT and GSH (Khan et al, 2021). PT was reported to alleviate diquat‐induced jejunum damage of chicken via regulating redox status mediated by Nrf2 and ferroptosis (Chen et al, 2023). Notably, Meng et al demonstrated that resveratrol supplementation during pregnancy and lactation upregulated the protein expression of Sirt1, enhanced the gene expression of antioxidant defence system related to Keap1 ‐ Nrf2 ( CAT , GPX , SOD1 , HO‐1 , GCLM , MGST1 , and UGT1A1 ) in placenta, which is similar to the PT action way in this study.…”

The Effects of Dietary Pterostilbene on the Immune Response, Antioxidant Function, and Jejunal Structure of Broilers

“…Therefore, maintaining intestinal health is crucial for promoting the efficient performance of animal production [19,20]. Some reports found that PTE and resveratrol supplementation in diet improved the structure and function of the intestinal mucosal barrier in animals [21,22]. Zhang et al found that dietary PTE and resveratrol effectively reduced the diamine oxidase (DAO) activity and D-lactate content in the damaged intestine of weaning piglets, with PTE having a more significant effect than resveratrol.…”