Efficacy of sodium butyrate in alleviating mammary oxidative stress induced by sub-acute ruminal acidosis in lactating goats.

Sub-acute ruminal acidosis (SARA) [1] is one of the most common problems of dairy animals causing great economical loss due to decreased milk production. Here we determined the antioxidant effect of sodium butyrate (NaB) [2] in experimentally induced SARA and its effects on mammary epithelial tissues of goat. Goats (n = 12) were equally divided into two groups: high-concentrate (HC) as control group fed with HC diet (concentrate: forage = 6:4) whereas HC + NaB as treatment group fed HC diet with NaB at 1% by weight for 24 weeks. Mammary epithelial tissue samples were analyzed for the expression of genes and proteins responsible for oxidative stress as well as biochemical markers of antioxidant activity in the form of Reactive Oxygen Species (ROS). The total antioxidant capacity (T-AOC) of antioxidant enzymes was also calculated. Butyrate induced antioxidant effect by increasing mRNA and protein abundance of antioxidants in mammary gland of HC + NaB group compared to HC group. Likewise, the total antioxidant capacity (T-AOC) was significantly increased and Malondialdehyde (MDA) concentration was decreased in HC + NaB group compared to HC group. It is concluded that oxidative stress in mammary gland of goats induced by high concentrate diet was alleviated by NaB supplementation.

Overfeeding with a high-concentrate diet activates the NOD1-NF-κB signalling pathway in the mammary gland of mid-lactating dairy cows.

Long term high-concentrate (HC) diet feeding induces subacute ruminal acidosis (SARA), which is reported to trigger a pro-inflammatory response. This study aimed to investigate the role of nucleotide-binding oligomerization domain protein 1 (NOD1) in initiating the pro-inflammatory response triggered by grain-induced SARA in the mammary gland of mid-lactating dairy cows. Twelve multiparous mid-lactating Holstein cows (455 ±â€¯28 kg) were randomly assigned into two groups to conduct the experiment for 18 weeks as follows: one group was fed a low-concentrate (LC) diet as a control (40% grain), and the other was fed an HC diet as a treatment (60% grain). Overall, the results showed that a decreased rumen pH and elevated γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP) concentrations in the HC group compared with LC group. The concentration of pro-inflammatory cytokines, including interleukin (IL)-1ß, IL-6 and tumour necrosis factor-alpha (TNF-α), significantly increased in the lacteal vein of the HC group than LC group. The mRNA expression levels of NOD1, receptor-interacting protein2 (RIP2), NF-κBp65 (p65), IL-1ß, IL-6, IL-8 and TNF-α, which involved in inflammatory response, were up-regulated in the HC-induced mammary gland. The changes of the target proteins, including NOD1, p65 and pp65 presented the same tendency as those of the target genes. Collectively, long-term high concentrate feeding-induced SARA increased the rumen iE-DAP concentration which activated NOD1-NF-κB signalling pathway-dependent inflammation in the mammary gland of mid-lactating cows.

Sodium butyrate improves antioxidant stability in sub-acute ruminal acidosis in dairy goats.

BACKGROUND: Currently, little is known about the effect of sodium butyrate (NaB) on oxidative stress following grain-induced sub-acute ruminal acidosis in dairy goats. In the present study, 18 lactating dairy goats implanted with a ruminal cannula and permanent indwelling catheters in the portal and hepatic veins were randomly allocated into 3 treatment groups over 20 weeks: low grain (LG, 40% grain; n = 6), high grain (HG, 60% grain; n = 6) and high grain with sodium butyrate (HG + NaB, 60% grain + NaB; n = 6). RESULTS: When added to the HG diet, NaB increased the mean ruminal pH and reduced the levels of ruminal, portal and hepatic LPS; Additionally, we observed an increase in SOD1, SOD2, SOD3, GPX1 and CAT mRNA expression, increased levels of TSOD and CAT enzyme activity as well as increased total antioxidant capacity (T-AOC) and decreased malondialdehyde (MDA) in both the liver and plasma, while GPx activity increased in the liver of goats fed the HG + NaB diet. The mRNA expression of UGT1A1, NQO1, MGST3, and Nrf2, as well as total Nrf2 protein levels were increased in goats fed the HG + NaB diet. CONCLUSIONS: Our study indicates that sodium butyrate could improve the oxidative status in sub-acute ruminal acidosis through the partial activation of Nrf2-dependent genes.

NOD1/NF-κB signaling pathway inhibited by sodium butyrate in the mammary gland of lactating goats during sub-acute ruminal acidosis.

Animals nurtured with a high-concentrate diet for a more extended period can cause subacute ruminal acidosis (SARA). In this study, twelve mid-lactating goats were separated into two groups (n = 6): a high concentrate diet (HC) control and a high concentrate with buffer (HCB) treatment group. Rumen fistula was installed in all lactating goats in the 14th week of the experiment. Goats were slaughtered in the 24th week. Our results showed that a pH value < 5.8 sustained at different periods of time for more than 3 h/day in the group HC, which confirms that SARA was prompted efficiently. Additionally, the group HCB exhibited lower concentration of LPS in peripheral blood than the group HC. Radioimmunoassay revealed a substantial reduction in the concentration level of proinflammatory cytokines in the lacteal blood of the group HCB compared to group HC. The transcriptional profiles in mammary gland following different treatments showed a significant decrease in the expression of NOD1, IKß, and NF-κB in HCB group, followed by a decreased transcriptional level of (TNF-α, IL-1ß and IL-6). Our research explores that HC diet nurtured to lactating goats for a more extended period can induce SARA by increasing the LPS and proinflammatory cytokine concentrations in plasma, that ultimately triggers the NOD1/NF-κB inflammatory pathway and induce mammary cell inflammation. Additionally, oral supplementation of sodium butyrate can decrease the concentrations of LPS and proinflammatory cytokines and inhibits NOD1/NF-κB inflammatory pathway.

Rumen-derived lipopolysaccharide provoked inflammatory injury in the liver of dairy cows fed a high-concentrate diet.

Rumen-derived lipopolysaccharide (LPS) is translocated from the rumen into the bloodstream when subacute ruminal acidosis (SARA) occurs following long-term feeding with a high-concentrate (HC) diet in dairy cows. The objective of this study was to investigate the mechanism of inflammatory responses in the liver caused by HC diet feeding. We found that SARA was induced in dairy cows when rumen pH below 5.6 lasted for at least 3 h/d with HC diet feeding. Also, the LPS levels in the portal and hepatic veins were increased significantly and hepatocytes were impaired as well as the liver function was inhibited during SARA condition. Meanwhile, the mRNA expression of immune genes including TNF receptor associated factor 6 (TRAF6), nuclear factor-kappa B (NF-κB), p38 mitogen-activated protein kinase (MAPK), extracellular regulated protein kinases (ERK) MAPK, Interleukin-1 (IL-1) and serum amyloid A (SAA) in the liver were significantly increased in SARA cows. Moreover, the phosphorylation level of NF-κB p65 and p38 MAPK proteins in the liver and the concentration of Tumor Necrosis Factor (TNF-α), Interleukin-1ß (IL-1ß) and Interleukin-6 (IL-6) in peripheral blood were obviously increased under SARA condition. In conclusion, the inflammatory injury in the liver caused by LPS that traveled from the digestive tract to the liver through the portal vein after feeding with a HC diet.

Sodium Butyrate Ameliorates High-Concentrate Diet-Induced Inflammation in the Rumen Epithelium of Dairy Goats.

To investigate the effect of sodium butyrate on high-concentrate diet-induced local inflammation of the rumen epithelium, 18 midlactating dairy goats were randomly assigned to 3 groups: a low-concentrate diet group as the control (concentrate:forage = 4:6), a high-concentrate (HC) diet group (concentrate:forage = 6:4), and a sodium butyrate (SB) group (concentrate:forage = 6:4, with 1% SB by weight). The results showed that, with the addition of sodium butyrate, the concentration of lipopolysaccharide (LPS) in rumen fluid (2.62 × 104 ± 2.90 × 103 EU/mL) was significantly lower than that in the HC group (4.03 × 104 ± 2.77 × 103 EU/mL). The protein abundance of pp65, gene expression of proinflammatory cytokines, and activity of myeloperoxidase (MPO) and matrix metalloproteinase (MMP)-2,9 in the rumen epithelium were significantly down-regulated by SB compared with those in the HC group. With sodium butyrate administration, the concentration of NH3-N (19.2 ± 0.890 mM) in the rumen fluid was significantly higher than that for the HC group (12.7 ± 1.38 mM). Severe disruption of the rumen epithelium induced by HC was also ameliorated by dietary SB. Therefore, local inflammation and disruption of the rumen epithelium induced by HC were alleviated with SB administration.

Lipopolysaccharide derived from the digestive tract triggers an inflammatory response in the uterus of mid-lactating dairy cows during SARA.

BACKGROUND: The aims of the current study were to evaluate the inflammatory response in cow uterus and to explore the molecular mechanism triggered by high concentrate-induced subacute ruminal acidosis (SARA) in mid-lactating dairy cows. Twelve mid-lactating Holstein cows with an average weight of 455 kg were allocated into two groups subjected to two diets for 18-weeks either a low-concentrate (LC) group containing 4:6 (NDF: NFC) and a high-concentrate (HC) group containing 6:4 (non-forage carbohydrates, NFC): (neutral detergent fiber, NDF) ratio based on dry matter. RESULTS: The HC group showed lower ruminal pH and higher lipopolysaccharide (LPS) concentrations in both the rumen and peripheral plasma compared to the LC group. The LPS concentrations in the rumen fluid and the peripheral plasma were found significantly increased in the HC group compared to the LC group. The concentrations of IL-1ß, TNF-α and IL-6 were significantly higher in the HC group compared to the LC group. The uterus of SARA cows revealed elevated mRNA concentrations of nuclear transcription factors and pro-inflammatory cytokines, which confirmed the presence of inflammation. The occurrence of uterine inflammation was further validated by the increased protein expression of NF-κB-p65 and its active phosphorylated variant in the uterus of SARA cows. Similarly, the inflammatory genes TLR4, LBP, MyD88, TRAF-6, NF-κB, IL-6, IL-8, TNF-α and IL-1ß were significantly upregulated in the uterus of the HC versus the LC group. CONCLUSION: Therefore, the results indicated that LPS derived from the rumen triggered the genes associated with inflammation in the uterus of mid-lactating dairy cows fed a high-concentrate diet, causing endometritis.