Effects of spermine on liver barrier function, amino acid transporters, immune status, and apoptosis in piglets

Abstract

This study investigated the effects of spermine supplementation and its extended duration on amino acid transporters, immune status, barrier function, and apoptosis in the liver. Eighty piglets were randomly assigned to a group receiving either a diet supplemented with spermine (0.4 mmol kg^-1 of body weight) or a restricted nutrient intake supplemented with saline in pairs for 7 h, 3 days, 6 days, and 9 days. Regardless of treatment time, spermine increased the levels of amino acid transporters, immunoglobulin M, antimicrobial peptides, cellular immune components, anti-inflammatory cytokines, mammalian target of rapamycin, ribosomal protein S6 kinase 1, signal transducer and activator of transcription 2 and 3, Janus kinase 2, zonula occludens 1 and 2, occluding, claudin-1, claudin-2, claudin-16 and Bcl-2 mRNA levels, whereas it decreased the levels of pro-inflammatory cytokines, inducible nitric oxide synthase, nuclear factor-kappa B P65, eukaryotic IF4E-binding protein 1, myosin light chain kinase, Bax, and caspase-3 mRNA in the liver (P < 0.05). These effects were also found in cases of prolonged spermine intake (P < 0.05). Spermine can decrease pro-inflammatory cytokines and caspase-3 levels. In conclusion, spermine may promote barrier function and improve amino acid transport, and can increase immune status and inhibit apoptosis in the liver.

Fig. 1. Effect of spermine on the gene expression of immune-related genes. Pigs fed with spermine (spermine groups) or saline (control groups) for 7 hours, 3 days, 6 days and 9 days, respectively. The relative mRNA expression levels of mTOR (a), S6K1 (b), 4EBP1 (c), NF-κB P65 (d), STAT2 (e), STAT3 (f) and JAK2 (g) in the liver of piglets. The values are the means ± standard error of the mean (n = 6). The different superscript letters (a, b, c, d) above the bars show significant differences at P < 0.05. mTOR, mammalian target of rapamycin; S6K1, ribosomal protein S6 kinase 1; 4EBP1, eukaryotic IF4E-binding protein 1; NF-κB P65, nuclear factor-kappa B P65; JAK2, Janus kinase 2; STAT3, signal transducer and activator of transcription 3; STAT2, signal transducer and activator of transcription 2.

Fig. 2. Effect of spermine on the gene expression of apoptosis-related genes. Pigs fed with spermine (spermine groups) or saline (control groups) for 7 hours, 3 days, 6 days and 9 days, respectively. The relative mRNA levels of Bax (a), Bcl-2 (b) and caspase-3 (c) in the liver of piglets. The values are the means ± standard error of the mean (n = 6). The different superscript letters (a, b, c, d, e) above the bars show significant differences at P < 0.05. Bax and Bcl-2, apoptosis related factor.