The present study was to investigate the protective effects of resveratrol (RSV) and its 3,5-dimethylether derivative pterostilbene (PT) against liver injury and immunological stress of weaned piglets upon lipopolysaccharide (LPS) challenge. Seventy-two weaned piglets were divided into the following groups: control group, LPS-challenged group, and LPS-challenged groups pretreated with either RSV or PT for 14 d (n = 6 pens, three pigs per pen). At the end of the feeding trial, piglets were intraperitoneally injected with either LPS or an equivalent amount of sterile saline. After 6 h of sterile saline or LPS injection, plasma and liver samples were collected. LPS stimulation caused massive apoptosis, activated inflammatory responses, and incited severe oxidative stress in the piglet livers while also promoting the nuclear translocation of nuclear factor kappa B (NF-κB) p65 (P < 0.001) and the protein expression of Nod-like receptor pyrin domain containing 3 (NLRP3; P = 0.001) and cleaved caspase 1 (P < 0.001). PT was more effective than RSV in alleviating LPS-induced hepatic damage by decreasing the apoptotic rate of liver cells (P = 0.045), inhibiting the transcriptional expression of interleukin 1 beta (P < 0.001) and interleukin 6 (P = 0.008), and reducing myeloperoxidase activity (P = 0.010). The LPS-induced increase in hepatic lipid peroxidation accumulation was also reversed by PT (P = 0.024). Importantly, inhibiting protein phosphatase 2A (PP2A) activity in a hepatocellular model largely blocked the ability of PT to prevent tumor necrosis factor alpha-induced increases in NF-κB p65 protein phosphorylation (P = 0.043) and its nuclear translocation (P = 0.029). In summary, PT is a promising agent that may alleviate liver injury and immunological stress of weaned piglets via the PP2A/NF-κB/NLRP3 signaling pathway.
Keywords: hepatic injury; immunological stress; lipopolysaccharide; piglet; pterostilbene; resveratrol.
Intensive swine production increases the exposure risk of piglets to immunological stress that disrupts hepatic functionality, leading to inferior disease resistance and compromised growth performance. Therefore, it is imperative to seek appropriate nutrients with protective potential to alleviate liver injury of young piglets under the conditions of immunological stress. The objective of this study was to investigate the potential of resveratrol and its derivative pterostilbene (PT) to protect the liver from lipopolysaccharide (LPS)-induced immunological stress and inflammatory damage in weaned piglets. In the animal study, PT exhibited significantly better efficacy than its parent compound in alleviating LPS-induced hepatic damage, probably by inhibiting nuclear factor kappa B (NF-κB) p65 nuclear translocation, Nod-like receptor pyrin domain containing 3 (NLRP3) and cleaved caspase-1 protein expression, and proinflammatory mediator overproduction. Under cell culture condition, inhibiting protein phosphatase 2A (PP2A), a negative regulator of the NF-κB signaling pathway, largely blocked the ability of PT to prevent NF-κB activation, indicating that PT may inhibit NF-κB signals in a PP2A-dependent manner. This study provides novel evidence that PT could serve as a hepatoprotective agent to alleviate hepatic damage and immunological stress in LPS-challenged piglets.
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