Effects of Continuous LPS Induction on Oxidative Stress and Liver Injury in Weaned Piglets

Simple Summary Pigs have been evaluated as good model animals for human physiological and pathological research. During the weaned period, piglets are vulnerable to pathogens due to the transformation from a liquid to a solid feed, environmental changes, and an immature autoimmune system. Intraperitoneal injection of lipopolysaccharide (LPS) has been widely applied to simulate liver injury in piglets, but there are still some puzzles and gaps in our understanding. Therefore, we explored the effects of continuous low-dose LPS induction on serum enzyme activity, antioxidant level, liver morphology, and mRNA expression related to liver injury in weaned piglets. The findings demonstrated that oxidative damage and liver injury occurred at the early stage with LPS induction, but the damage was gradually weakened at the later stage. This indicated that continuous LPS induction may cause endotoxin tolerance after a certain amount of time. Due to imperfections in their immune and digestive systems, weaned piglets are susceptible to invasions of the external environment and diseases, especially bacterial infections, which lead to slow growth, tissue damage, and even the death of piglets. Here, a model of weaned piglets induced by Escherichia coli lipopolysaccharide (LPS) was established to explore the effects of continuous low-dose LPS induction on the mechanism of liver injury. A total of forty-eight healthy 28-day-old weaned piglets (weight = 6.65 +/- 1.19 kg) were randomly divided into two groups: the CON group and LPS group. During the experimental period of thirteen days, the LPS group was injected intraperitoneally with LPS (100 mu g/kg) once per day, and the CON group was treated with the same volume of 0.9% NaCl solution. On the 1st, 5th, 9th, and 13th days, the serum and liver of the piglets were collected for the determination of serum biochemical indexes, an antioxidant capacity evaluation, and histopathological examinations. In addition, the mRNA expression levels of the TLR4 pathway and inflammatory cytokines were detected. The results showed that the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in the serum increased after LPS induction. The activities of total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px) in the serum and liver homogenate of the LPS group were lower than those of the CON group, while the malondialdehyde (MDA) content in the serum and the activities of catalase (CAT) and superoxide dismutase (SOD) in the liver of the LPS group were higher than those in the CON group. At the same time, morphological impairment of the livers occurred, including hepatocyte caryolysis, hepatocyte vacuolization, karyopycnosis, and inflammatory cell infiltration, and the mRNA expression levels of TLR4, MyD88, NF-kappa B, TNF-alpha, IL-6, and IL-10 were upregulated in the livers after LPS induction. The above results were more obvious on the 1st and 5th days of LPS induction, while the trend during the later period was not significant. It was concluded that the oxidative stress and liver injury occurred at the early stage of LPS induction, while the liver damage weakened at the later stage. The weaned piglets probably gradually developed tolerance to the endotoxin after the continuous low-dose induction of LPS.

Automated summary

Continuous low-dose lipopolysaccharide (LPS) induction in weaned piglets causes oxidative damage and liver injury at the early stage, but the damage weakens over time, indicating the development of endotoxin tolerance. Weaned piglets are susceptible to external environment and diseases, especially bacterial infections, which affect their growth and lead to tissue damage or death. This study examines the effects of continuous low-dose LPS induction on liver injury mechanisms in weaned piglets using an Escherichia coli LPS-induced model.