Reuterin is well-known for its broad-spectrum antimicrobial ability, while the other potential bioactivity is not yet clear. The present study aims to investigate the immunomodulatory activity of reuterin on chicken macrophage HD11 cells for the first time and evaluate whether reuterin is able to regulate the lipopolysaccharide-stimulated inflammatory response. The results showed that the safe medication range of reuterin was less than 250 μM. Reuterin treatment for 6 h decreased the transcriptional of CD86, IL-1β and iNOS and increased the expression of CD206 in a dose-dependent way, but reuterin treatment for 12 h contrary increased the expression of IL-1β, IL-6 and IL-10. However, it was noticed that reuterin treatment for 12 h significantly decreased the production of reactive oxygen species (ROS) and suppressed the phagocytosis activity of HD11 macrophages against bacteria. Further, the results showed that preincubation or coincubation with reuterin significantly attenuated the promotive effects of lipopolysaccharide (LPS) on transcription of proinflammatory cytokines (including IL-1β, IL-6 and TNF-α) and obviously inhibited nitric oxide (NO) production as well as the protein expression of inducible nitric oxide synthase (iNOS). Meanwhile, Mechanism studies implied that reuterin might exert an anti-inflammatory effect on LPS-stimulated cells by downregulating the expression of TLR4/MyD88/TRAF6 and blocking the activation of NF-κB as well as MAPKs signaling pathways. Additionally, it was found that both pretreatment and cotreatment with reuterin remarkably inhibited the oxidative stress induced by LPS stimulation by activating the Nrf2/HO-1 signaling pathway and enhancing the activities of antioxidative enzymes. These findings suggested the immunoregulatory function of reuterin and indicated this bacterial metabolite was able to inhibit the inflammation and oxidative stress of HD11 macrophages once exposed to LPS stimulation.

Environmental factors such as high temperature can cause oxidative stress and negatively affect the physiological status and meat quality of broiler chickens. The study was conducted to evaluate the effects of dietary maternal Zn-Gly or ZnSO₄ supplementation on embryo mortality, hepatocellular mitochondrial morphology, liver antioxidant capacity and the expression of related genes involved in liver oxidative mechanisms in heat-stressed broilers. A total of 300 36-week-old Lingnan Yellow broiler breeders were randomly divided into three treatments: (1) control (basal diet, 24 mg zinc/kg); (2) inorganic ZnSO₄ group (basal diet +80 mg ZnSO₄/kg); (3) organic Zn-Gly group (basal diet +80 mg Zn-Gly/kg). The results show that maternal zinc alleviated heat stress-induced chicken embryo hepatocytes’ oxidative stress by decreasing the content of ROS, MDA, PC, 8-OHdG, and levels of HSP70, while enhancing T-SOD, T-AOC, CuZn-SOD, GSH-Px, CTA activities and the content of MT. Maternal zinc alleviated oxidative stress-induced mitochondrial damage in chick embryo hepatocytes by increasing mitochondrial membrane potential and UCP gene expression; and Caspase-3-mediated apoptosis was alleviated by increasing CuZn-SOD and MT gene expression and decreasing Bax gene expression and reducing the activity of caspase 3. Furthermore, maternal zinc treatment significantly increased Nrf2 gene expression. The results above suggest that maternal zinc can activate the Nrf2 signaling pathway in developing chick embryos, enhance its antioxidant function and reduce the apoptosis-effecting enzyme caspase-3 activities, thereby slowing oxidative stress injury and tissue cell apoptosis.